Grooming Behaviors

Definition

Grooming refers to the cleaning that a mouse does on its (or another mouse’s) fur and body. 

Grooming behaviors are typically classified as maintenance behavior since they serve to keep a mouse’s appearance, homeostasis, and cleanliness.   

Since grooming is an active behavior, it can be observed when a mouse is active during the awake-phase. In some cases, grooming may also be an abnormal behavior, an agonistic behavior, or a sexual behavior. 

Overview/Description 

Grooming is a broad behavioral category that is composed of many different subtypes of grooming behaviors. Each of these grooming behaviors has its own distinguishable characteristics and contexts in which it is likely to appear. 

Related Behaviors  

Grooming behaviors are comprised of other behaviors, such as nibble and lick, which are at the core of keeping the mouse clean. Important behaviors which are related to grooming include: 

• Nibble. A mouse nibbles its fur and/or skin by lightly pricking it with its teeth. Nibbling its skin and coat enables the mouse to clean itself thoroughly. 
• Scratch. A mouse will perform scratching motions using its forelimbs or hindlimbs in order to alleviate the feeling of itchiness. 
• Lick. Using its tongue, a mouse will lick over its fur and body as a means of washing itself.  
• Bite. In the case of abnormal or aggressive forms of grooming behaviors, a mouse may bite itself or another mouse and subsequently remove fur and/or whiskers.

Types of Grooming Behaviors

Many allogrooming behaviors exist. They are distinguished based on the situation and context that they appear in. 

• Allogrooming. Allogrooming is performed between two mice, thus is an affiliative behavior. One mouse will groom and clean the fur of another mouse while the other mouse is still and receptive to the actions. A variant of allogrooming is vigorous allogrooming wherein the dominant mouse is grooming the recipient mouse vigorously, with a lot of power and energy. 

Table of Contents

• Definition
• Description
• Related Behaviors
• Types of Grooming Behaviors
• Function of Grooming Behaviors
• Application of Grooming
• Research Techniques
• Behavioral Tests
• Pharmaceutical Studies
  • Allogrooming and Pharmaceutical Studies
  • Barbering and Pharmaceutical Studies
  • Cephalocaudal Grooming and Pharmaceutical Studies
  • Self-Grooming and Pharmacological Findings
• Mouse Strains Exhibiting Grooming Behaviors
  • Allogrooming Across Mouse Strains
  • Barbering in Mouse Strains
  • Cephalocaudal Grooming Across Mouse Strains
  • Self-Grooming Across Mouse Strains
• Abnormalities of Grooming Behaviors
  • Allogrooming Abnormalities
  • Cephalocaudal Grooming Abnormalities
  • Self-Grooming Abnormalities
• Disease Models of Grooming Behaviors
  • Allogrooming Disease Models
  • Barbering Disease Models
  • Cephalocaudal Grooming Disease Models
  • Self-Grooming Disease Models
• Summary
• References

Function of Grooming Behaviors

Grooming takes up a lot of a mouse’s time, thus, it is an important behavior during the awake phase. Grooming has multiple adaptive functions, including: 

• Decreasing pain. Self-grooming may be used as a way to decrease pain due to its self-soothing properties. Being able to reduce pain is an evolutionarily useful trait because it enables faster healing and less time spent in a sub-optimal state, thus able to sustain other behaviors necessary for maintaining life. 
• Maintaining thermoregulation. When a mouse is self-grooming it isn’t just cleaning itself, but it is also controlling its body temperature. Since self-grooming is a means of regulating body temperature, it is essential for homeostasis and survival. When self-grooming, the mouse will cover its fur with saliva which, when it evaporates, will cool off the mouse. 
• Maintaining body care and hygiene levels. Since hygiene is extremely important for health and survival, grooming behaviors like self-grooming, cephalocaudal grooming, and allogrooming, all keep a mouse’s hygiene levels at an optimum level, and are associated with health and well-being.
• Controlling louse population. In the instances of self-grooming and allogrooming, louse populations are controlled because the mice are able to groom themselves and rid themselves of parasites. When self-grooming, the mouse can only clean its body, but when allogrooming, the louse from the head and neck can be removed. Thus, these two grooming behaviors complement each other in order to keep the mouse colony free from lice which is beneficial because it enables them to stay healthy and disease-free.
• Gaining dominance. Social barbering is commonly exerted in order to establish dominance status over other mice. In fact, dominant mice are likely to barber other cagemates which are not as dominant. (But, if a dominant mouse is barbered, it does not alter their inherent levels of social dominance.) 
• To promote group cohesiveness. Allogrooming has the purpose of reinforcing a group’s cohesiveness. Through allogrooming, a sense of affiliation can be created wherein the mice become more familiar with one another, thus leading to group cohesiveness. Such a social environment is healthy and evolutionarily useful because it provides the mouse a sense of belonging, well-being, and safety. 
• To strengthen existing bonds. Also, allogrooming has the ability to strengthen existing bonds, in addition to instilling group cohesiveness. While group cohesiveness is generally promoting the well-being of the entire group, strengthening existing bonds can refer to the relationship between specific mice belonging to the group.  
• To identify potential sexual partners. Allogrooming may even be useful in terms of reproduction when it is occurring between male and female mice. The allogrooming interaction can serve as an introduction which would lead to a possible future sexual partnership between the two mice. 
• To attend to the offspring’s hygiene. Mothers that allogroom their pups are essentially providing a layer of defense for their offspring. Since saliva has antibacterial properties, licking pups provide an adaptive value which increases survival by protecting their pups against pathogens. Since pups do not have a fully developed immune system, a mother’s saliva (which contains antimicrobial properties) acts as a shield of immunity. 

Application of Grooming

Grooming behaviors can be observed under the following scenarios: 

• In response to stress. Many of the different types of grooming behaviors occur in response to stress. For example, cephalocaudal grooming is triggered by high levels of circulating corticotropin-releasing hormone (CRH) in response to stress. In fact, researchers may subject a mouse to environmental stressors or chronic stress models, in order to study grooming behaviors and compare its manifestation with non-stressed controls. 
• When restoring cleanliness. When a mouse gets dirty, it will begin cleaning or grooming itself in an effort to restore its cleanliness. 
• After copulation. In the case of post-copulatory grooming, male mice can be observed grooming their anogenital region after copulation. 
• While self-grooming. While self-grooming, a form and sequence of grooming, namely, cephalocaudal grooming, can be observed. The mouse grooms itself following a strict sequence or pattern beginning from the face, continuing to the body, then finishing at the tail.
• In a social context. As in the case of allogrooming where one mouse cleans and grooms another mouse, grooming can be observed between two mice when they are in the presence and close proximity to each other. 
• While huddling. Huddling involves many mice being in close proximity to one another or even on top of each other. Allogrooming can be observed while mice are huddling together because such close proximity (combined with a mouse’s natural social inclination) is likely to trigger the behavior. Check out our article on huddling. 
• In a social grouping. Social grouping, a living condition where mice are living together for a prolonged period of time is bound to trigger grooming behaviors, such as allogrooming or even barbering, since these grooming behaviors require an actor and a recipient. 
• During nursing. When mothers are weaning and nursing their young, they will hold and lick their pup, thus allogrooming. Even in communal nursing where many mothers are simultaneously raising and caring for their young, allogrooming is still bound to occur.  

Research Techniques 

In order to study grooming behaviors, research techniques must be employed based on the experimental question or variable of interest. These techniques and methods are used for studying grooming behaviors:

• Behavioral studies. Behavioral studies are very useful for studying grooming behaviors because they enable the researcher to profile, describe, and quantitatively assess grooming behaviors across mouse strains and interventions. 
• Pharmaceutical studies. Pharmaceutical studies are used when studying the effect of certain drugs or supplements on grooming behaviors. This is done in order to determine how a drug will affect the manifestation of a specific grooming behavior.  
• Genetic studies. Genetic studies are useful for identifying potential genes involved in grooming behaviors. This type of study is particularly useful when considering the abnormal forms of grooming behaviors. 

Behavioral Tests

Behavioral tests are used in behavioral studies as a means of determining and quantifying grooming behavior in mice under certain experimental conditions. The following behavioral tests are used to study mice’s grooming behaviors: 

• Adhesive Tape Removal. In the Adhesive Tape Removal Test, adhesive tape is placed on the mouse’s body. The mouse feels this and tries to remove the tape through grooming behaviors. Therefore, this test is used as a means of identifying how intact the mouse’s grooming abilities are. 
• Social Interaction Test. The Social Interaction Test is useful for observing grooming behaviors which happen in a social context. In this test, two mice are placed together in the same cage and their behavior is observed. Allogrooming and cagemate barbering, since they are types of grooming behaviors which occur in a social context, are likely to be observed within a social interaction between two mice.  
• Three-Chamber Test. The three-chamber test, sometimes referred to as the Sociability Chamber, is used to evaluate cognition expressed through general sociability using both familiar and novelty mice. A mouse will spend more time exploring a novelty mouse in the chamber than it will spend exploring a familiar one. This test helps in identifying deficits related to sociability in mice. Even though the three-chamber test is reserved for studying social interaction, grooming behaviors will naturally be expressed during the observation period and a researcher may choose to quantify them as a part of their analysis. 
• The Spray Test. In the spray test, a mouse is sprayed once with a mist of water. Then, it is placed in a clean cage with ad-lib water and food available to them. After this, its behavior is recorded for 15 minutes. The video will be analyzed by viewers who are trained to assess specific forms of grooming behaviors. Sometimes, the protocol may vary and a mouse will be sprayed 3 times (instead of once) and placed in plastic cylinders (instead of cages) in order for grooming to be analyzed. The spray test is a simple way to elicit grooming behaviors in an experimental setting where water is the stimulus that triggers the behavior. 
• Video Analysis. Video analysis is used in studying the different types of grooming behaviors. By capturing video footage of the mouse, specific details can be focused on which otherwise may have gone unnoticed during real-time observation. Video analysis offers the researcher control over the video, thus enabling detailed behavioral recording.   
• The Visible Burrow System. This test uses a cage designed to mimic mice’s natural environment. Its arrangement has an open area linked side panels which resemble runnels, thus creating an environment optimal for a wide range of behaviors to occur. Before an experiment begins, mice are individually labeled or marked with hair dye and introduced to the setting at the beginning of their dark cycle. A video recording system is used to capture the mice’s behaviors over a long period of time. Some experiments which use the visible burrow system can last for weeks.  
• The Open Field Test. In the Open Field Test, mice are placed in a cage that is closed at the sides (in order to prevent escape) but open from above. This test is used in order to investigate anxiety and exploratory behaviors. Some research studies utilizing the Open Field Test may take note of instances of self-grooming behaviors if they occur during the observational period. 
• The Elevated Plus-Maze. The Elevated Plus-Maze is a behavior test that is a gold standard for behavioral research which focuses on anxiety. By using this test, the mouse is introduced to an anxiety-causing situation and its behavioral responses are subsequently studied and recorded. Since self-grooming can be triggered by anxiety, some experiments which use the Elevated Plus-Maze to study a mouse’s anxiety-related behaviors will also take note of its grooming profile. The maze is set up to have 4 arms, two open and two closed arms. 
• The Tube Dominance Test. Social or cagement barbering can be observed in an agonistic setting, such as the ones created in the Tube Dominance Test. In this test, two mice are placed in a tube from either end and can only move forwards. 
• The Resident-Intruder Test. In this test, when an unknown mouse is placed in the cage in which a single mouse resides, an agonistic encounter is extremely likely to occur. In this case, barbering may be performed by the more dominant mouse. 

Pharmaceutical Studies

Allogrooming and Pharmaceutical Studies

• Sodium valproate decreases allogrooming. A commonly used mouse model of autism in behavioral research is induced via valproate (VPA) injections. Children that have had in utero exposure to VPA develop fetal valproate syndrome which is a syndrome that shares symptoms with autism, including: language and communication deficits, stereotypic behavior, delays in development, and hyperexcitability. In fact, just a single dose of 400 mg/kg VPA on postnatal day 14 (which is equivalent to the human third trimester) is enough to induce an autism model in BALB/c mice. Since autism is associated with social deficits, affiliative behaviors are affected. In mice, this is observed as a reduction in allogrooming behaviors. Mice induced with autism via VPA injections have decreased allogrooming and anogenital sniffing, both of which are affiliative forms of interaction. 
• XAV939 injection decreases allogrooming in mice. XAV939 is a small compound that can be administered to developing embryonic mice via in utero injections. XAV939 affects mouse development, including the way that the neocortex forms, which, in turn, later affects observable behaviors such as self-grooming. Mice that receive XAV939 injections in utero have increased levels of the Axin protein in radial glia cells. Such high levels of Axin affect cellular processes and ultimately lead to heightened intermediate progenitors and thus excess levels of pyramidal neurons within the neocortex. Therefore, overproduction of pyramidal neurons in the neocortex as caused by XAV939 injections leads to a neocortical malfunction (due to malformation) which further affects observable behavior. Experimental mice injected with XAV939 display behavioral deficits resembling those found in autism, such as decreased social behaviors and increased repetitive behaviors. Mice receiving this injection spend significantly less time allogrooming and more time self-grooming. The low instances of allogrooming due to the XAV939 injection demonstrates how malformation in high-order brain regions such as the neocortex can cause an imbalance in excitatory and inhibitory brain systems. 
• Oxytocin antagonist may increase vigorous allogrooming. Oxytocin is a neuropeptide that is mostly produced by the supraoptic and paraventricular nuclei found in the hypothalamus. These neurons project to many different areas of the brain and secrete oxytocin. Research using mice has established that higher levels of oxytocin (achieved as a result of oxytocin administration) elicits more self-grooming behaviors in mice, but it is also possible that blocking or antagonizing central oxytocin pathways may lead to an increase in vigorous allogrooming, according to a 2015 behavioral study published by Arakawa et al. in the academic research journal Physiology and Behavior. 
• Allogrooming decreased by L-DOPA after social defeat experience. L-DOPA is an amino acid that is naturally produced in the body and a precursor to catecholamine neurotransmitters such as epinephrine (adrenaline), norepinephrine, and dopamine. In animal research, L-DOPA has been demonstrated to affect allogrooming behavior. Mice that have experienced social defeat and have been given L-DOPA will show decreased levels of allogrooming. On the other hand, mice that do not experience social defeat and are given L-DOPA will have the same levels of allogrooming behavior as control mice, thus remain unaffected. This interaction demonstrates the complex interrelationships between drugs and behaviors and how one environment or setting can increase or decrease allogrooming. 

Barbering and Pharmaceutical Studies

• Clomipramine reduces barbering in trichotillomania mice. Clomipramine is a tricyclic antidepressant which is able to inhibit serotonin reuptake system. Mice which have a genetic mutation that knockouts the nitric oxide synthase (NOS2) gene are used as an animal model of trichotillomania due to their high levels of barbering behavior. However, when given clomipramine, these mice will barber significantly less after 10-20 days of treatment when compared with untreated NOS2 mice. More information will be given about NOS2 mice in the upcoming Mouse Strains section.  
• Estradiol injections reduce barbering in trichotillomania mice. Trichotillomania, defined as repetitive hair-plucking, is related to Obsessive-Compulsive Disorder and is a common disorder in women. Not much is known regarding the disorder’s mechanisms and biological causes. In mice, barbering is a hair-plucking behavior that has been validated as a model for trichotillomania. Correlations have been found between the onset of trichotillomania and changes in reproductive physiology, leading to the hypothesis that reproductive hormones may play a role in the disease. Estrogen doses are able to influence the brain’s catecholamines and endogenous opiates which are known to regulate and interact with corticostriatal loops which are implicated in motor and planning behavior. 17β-estradiol benzoate injections reduce barbering in females when compared to females on a vehicle solution. The effect of estrogen injections implies that sex hormones are critical for determining the onset of trichotillomania.   

Cephalocaudal Grooming and Pharmaceutical Studies

• Diazepam enhances cephalocaudal grooming. Diazepam, a γ-aminobutyric acid (GABA)-ergic anxiolytic compound, when administered to mice can affect the cephalocaudal sequence by decreasing number of interrupted bouts and the overall percentage of incorrect transitions that a mouse performs when compared to a saline group. 
• Pentylenetetrazole affects cephalocaudal grooming. Pentylenetetrazole, a γ-aminobutyric acid GABAergic anxiogenic compound, is associated with ‘high arousal’ grooming patterns in mice. When given this drug, the mouse will become very energetic, have high interruptions in the cephalocaudal grooming sequence, and frequently display incorrect transitions. 
• Fluoxetine decreases cephalocaudal groom. Fluoxetine, commercially known as Prozac, is a selective serotonin reuptake inhibitor which can also affect the cephalocaudal grooming profile observed in mice. Fluoxetine decreases the total number of cephalocaudal grooming bouts and transitions.and patterns. 
• Amitriptyline decreases grooming. Amitriptyline, a drug used to treat numerous psychiatric conditions (including anxiety disorders and major depressive disorder), has been demonstrated to be able to reduce cephalocaudal grooming bouts, the average number of patterns displayed within a bout, as well as the transitions across cephalocaudal grooming stages in mice. 

Self-Grooming and Pharmacological Findings

• XAV939 Increases Self-Grooming. As mentioned previously XAV939 instigates the overproduction of pyramidal neurons in the neocortex thus leading to behavioral abnormalities. Experimental mice injected with XAV939 display behavioral deficits resembling those found in autism, such as excessive repetitive behaviors. Mice receiving this injection spend significantly more time self-grooming (and less time allogrooming). The high instances of self-grooming due to the XAV939 injection demonstrates how malformation in high-order brain regions such as the neocortex can cause an imbalance in excitatory and inhibitory brain systems, ultimately leading to the manifestation of repetitive behaviors. 
• Valproic acid increases repetitive self-grooming in mice. Valproic acid is a form of valproate and may be used as a medication to treat medical conditions such as epilepsy, bipolar disorder, and migraines. However, prenatal exposure to valproic acid has been demonstrated to be associated with an increased risk in autism. In animal research, mouse models of autism which were subjected to prenatal exposure to valproic acid are commonly used. In fact, mice that are exposed to valproic acid will demonstrate significantly higher levels of repetitive self-grooming than mice that are not exposed. The leading theory explaining this behavioral change states that valproic acid alters neuronal circuitry which ultimately leads to an imbalance between excitatory/inhibitory signaling, causing an increase in excitation and a decrease in inhibition. Thus, in terms of a mouse that has been exposed to valproic acid, high levels of excitation will be seen as higher frequencies and time spent self-grooming due to the inability to inhibit such actions. 
• Fluoxetine reduces elevated self-grooming in Ninj1 knockout mice. Fluoxetine is able to reduce elevated levels of self-grooming in mice with the Ninjurin 1 (Ninj1) cell adhesion molecule knocked out. (More specifics on this mouse strain can be found in the next section.) Ninj1 knockout mice lack a protein that is typically found on the cell membrane and involved in cell adhesion. Their behavioral phenotype includes high levels of self-grooming which results in progressive hair loss. Chronic treatment with fluoxetine, a drug that belongs to the selective serotonin reuptake inhibitor (SSRI) class and can be used for treating depression, has been shown to alleviate this mouse strain’s compulsive levels of self-grooming and is also able to decrease their high levels of anxiety-like behavior when given at a dose of 18 mg/kg via water for the span of 3 weeks.
• MPEP reduces repetitive self-grooming. Administration of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) leads to a reduction of repetitive self-grooming in BTBR mice, a particular mouse strain that is commonly used in animal research for the purposes of modeling autism spectrum disorders. MPEP is a mGluR5 metabotropic glutamate receptor antagonist. Since MPEP acts on mGluR5 receptors, it can affect the processes which mGluR5 receptors are involved in, including the regulation of N-methyl-D-aspartate (NMDA) receptors’ phosphorylation status and NMDA receptor-related neurotransmission. Thus, when BTBR mice are given MPEP there is a significant decrease in their high levels of self-grooming as a result. This change demonstrates that some alternation in NMDA receptors may be the reason that repetitive levels of self-grooming occur within the BTBR strain. Furthermore, MPEP administration is able to significantly decrease repetitive self-grooming in other mouse models of autism such as the commonly utilized valproic acid model. 

Mouse Strains Exhibiting Grooming Behaviors

The following section is organized by grooming behaviors. Under each sub-section, specific mouse strains are discussed in terms of the specific grooming behavior.

Allogrooming Across Mouse Strains

• BTBR mice have low allogrooming levels. BTBR T+tf/J (BTBR) mice demonstrate low levels of allogrooming which is in line with their general low-sociability behavioral phenotype. BTBR mice are an inbred mouse strain which are commonly used in behavioral studies for the purposes of modeling the diagnostic symptoms associated with autism. While BTBR mice have low levels of allogrooming and other social interaction behaviors such as social approach, they do not exhibit deficits in motor abilities nor high levels of anxiety-like behavior, meaning that their deficits are mainly specific to social disturbances.
• R1117X Mutant mice have increased levels of allogrooming behavior. The SHANK3 gene is implicated in having many different functions in the brains due to its structure complexity and thus is an important gene for optimum performance. SHANK3 abnormalities have also been identified in patients with autism spectrum disorder. Additionally, a mutation in SHANK3 wherein an arginine is changed to a stop-codon (R1117X) has been associated with schizophrenic patients. This demonstrates the phenomenon of how mutations in the same gene can be associated with different disorders. Mice with a R1117X mutation in the SHANK3 gene demonstrate increased levels of allogrooming behavior and have synaptic defects in the brain’s prefrontal cortex.
• NF-κB p50-deficient mice do not allogroom frequently. The nuclear factor (NF)-κB is a transcription factor that is crucial for cell survival and for regulating inflammatory immune responses. It has been demonstrated to be active in neurons. Mice with NF-κB lacking the subunit p50 perform poorly in cognitive tasks and also show less instances of allogrooming when compared to wild-type mice.
• C57B1/6J, BALB/CJ, and NIH subordinate mice allogroom. Across all three strains, allogrooming is much more frequent amongst subordinate mice (subordinate to subordinate) than any other combination (dominant to subordinate or subordinate to dominant). Furthermore, BALB/CJ and NIH mice have more allogrooming behaviors (performed between same-strain mice) than the C57B1/6J mice do.
• EN2-/- mice. In genetics research, the homeobox transcription factory (EN2) has been shown in human studies to be correlated with autism spectrum disorder (ASD) susceptibility. So, researchers are using EN2 -/- mice which lack EN2, in order to model ASD. One study showed that EN2 -/- mice had less instances of allogrooming when compared with the control group. Since allogrooming is a social behavior, this finding was interpreted to parallel the social deficits observed in humans with ASD. On a side note, the researchers also found that the ASD mice had difficulty in memory tasks, as shown from the data acquired by means of using the Morris Water Maze and increased latency times in each test trial, possibly implying a relationship between grooming, sociability, and memory abilities.

Barbering in Mouse Strains

• NMRI mice. NMRI mice have been used in behavioral research for almost a century now for general studies as well as for pharmacology or toxicology. NMRI mice are commonly used as a control or comparator breed but as they increase in age they may develop tumors spontaneously or even renal disease. Social barbering will be exhibited by NMRI mice even if they are housed together since weaning. Social barbering is common in the NMRI mice for both males and females. However, in same-sex cages, barbering is also associated with fighting in males, but not in females. If NMRI mice are socially housed together for the first time, barbering will still be observed within 2-5 days of grouping. Barbering within this strain is characterized by head and snout denuding, as well as whisker removal.
• C57BL/6 mice. C57BL/6 mice will begin to demonstrate social barbering at about 14 weeks of age. At 20 weeks of age, this strain will begin to demonstrate whisker-plucking specifically if housed in pens containing 8 mice or more. In general, C57BL/6 mice are regarded as a strain which demonstrates high levels of barbering and is usually used as a comparator strain in behavioral studies.
• 129S1 mice. 129S1/SvImJ mice, simply referred to as 129S1 mice, are commonly used as a background strain in behavioral research (as C57Bl/6 mice are) and are known for their anxiety-like behavioral tendencies and learning variabilities. Furthermore, 129S1 mice are also popular in behavioral research as they can be easily used to produce targeted mutations since they have multiple embryonic stem cells lines available. When it comes to barbering, 129S1 female mice are more likely to exhibit social barbering behaviors amongst each other than males under housing conditions, which include group housing since weaning.
• BALB/cJ mice. BALB/cJ male mice will begin to demonstrate whisker-picking at 10 weeks old, while female BALB/cJ mice at 12 weeks old (on average). This suggested a possible gender difference between BALB/cJ male and female mice with respect to the first manifestation of barbering behavior.
• PLCβ1 knockout mice. Schizophrenic patients have been reported to have reduced levels of phospholipase C (PLC) β1 in certain regions of the brain. In general, phospholipids, which are affected by this type of genetic abnormality, have an important neuro-architectural role. This is because they are necessary for the structure of neural membranes and efficient signal transduction which connect neuronal response and receptor occupancy. In humans, PLCβ1 has been found to be expressed in the hippocampus, cerebral cortex, amygdala, olfactory bulb, and lateral septum. Mice which have the PLCβ1 gene knocked have inhibition of the acoustic startle response and hyperactivity in the Open Field. These mice also have social abnormalities including low levels of sociability and low instances of barbering. Low levels of barbering is considered to be an abnormality since barbering is associated with the establishment of a social hierarchy. Thus, the lack of barbering (and thus, by extension, lack of hierarchy) is a peculiarity which may further reflect the schizophrenic phenotype described by a lack of social skills as expressed by social withdrawal and isolation.
• A2G mice. Barbering is found to increase as the A2G mice age. One experiment, conducted by Strozik and Festing, established that in about 75% of the cages which have 2-3 mice, there will be at least 1 active barber by the time the mice become 60 days old. In cages with male mice, there is usually one mouse with untrimmed whiskers, presumably the most dominant of the male mice. In contrast, several female mice are likely to be barbers within a cage. Current evidence is pointing in the direction that female A2G mice are sensitive to pregnancy and are less likely to be whisker-plucked by their cage mates if they are pregnant.
• AChe-/- mice. Acetylcholinesterase (AChE) is know to function in nerve impulse transmission and may even serve as a cell adhesion factor when there is neurite outgrowth occurring. This would theoretically imply that mice without AChE would not be able to live. However, AChE-/- knockout mice are, in fact, born alive and can survive for an average of 14 days. When these mouse strains are fed with a high fat diet, their lifespan can increase anywhere from 100 days to 15 months. Male mice which are fed on this diet will not be threatening or demonstrate aggression, but they will establish hierarchy and barber one another’s whiskers and fur across the face, shoulders, and back.
• NOS2 knockout mice. NOS2 knockout mice lack the nitric oxide synthase gene and have high levels of barbering as a result. These mice will demonstrate barbering in high instances by the time they become 4 weeks old. Their rate of barbering will continue to increase by the time they reach adulthood.
• GalNAc-4-ST1–/– mice. GalNAc-4-ST1–/– mice have a genetic mutation which ultimately affect their luteinizing hormone (LH). LH is an important hormone since it is crucial for the proper production of the sex hormones testosterone, estradiol, and progesterone. Therefore, any perturbation with this hormone can be associated with issues in sexual development and maturity. The structure of LH is such that it has a unique N-linked carbohydrate unite which ends with a sulfated N-acetylgalactosamine structure (GalNAc-4-SO4) that is important for clearing LH from the blood. In order to target this, researchers ablate the gene that encodes the sulfotransferase which is involved in adding the sulfate to the GalNAc found on the LH. In mice, this corresponds to the GalNAc-4-sulfotransferase-1 (GalNAc-4-ST1). GalNAc-4-ST1-/- mice have very high levels of barbering amongst one another. Since this genetically manipulated strain also has higher levels of testosterone than normal, they demonstrate early sexual maturation and higher aggressive behavior which is observed in the form of higher instances of barbering.
• S-COMT deficient mice. Catechol-O-methyltransferase (COMT) is responsible for catalyzing or breaking down the O-methylation of important catecholic compounds which are found in the brain, such as L-dopa, catecholamines, and also their hydroxylated metabolites. COMT is an enzyme which has two forms, either as soluble (S-COMT) or membrane-bound (MB-COMT) isoforms but both are known to be products which come from the same gene. Although, in rodents and humans, S-COMT is more available, in the human brain there is about a 2.5-fold higher amount of MB-COMT than S-COMT. It has been found that mice which lack both forms of COMT have a two-fold increase in the time it takes to eliminate dopamine from the prefrontal cortex. In S-COMT deficient mice, it has been established that subtle social interaction changes occur including increased barbering behavior and decreased sniffing time of another mouse.

Cephalocaudal Grooming Across Mouse Strains

• 129S1 mice demonstrate low grooming activity. The 129S1/SvImJ mouse strain is widely used in behavioral research, but has an impaired grooming microstructure, meaning that these mice have frequently interrupted bouts (pausing abruptly amidst grooming) and incorrect transitions (i.e. not following the cephalocaudal sequence).
• BALB/c and NMRI mice display normal cephalocaudal grooming patterns. Two other strains which are commonly used in behavioral research are the BALB/c and NMRI mouse strains. In contrast to the 129S1/SvImJ mouse strain, the BALB/c and NMRI mice show unimpaired, normal grooming patterns. The BALB/c strain is more active and likely to groom than the NMRI strain.

Self-Grooming Across Mouse Strains

• Ninj1 knockout mice. Abnormalities to the Ninjurin 1 (Ninj1) cell adhesion molecule is associated with an abnormal phenotype which affects behavior. Cell adhesion molecules are located on the cell membrane and are responsible for binding with the cellular matrix or with other cells, thus making cell adhesion possible. Therefore, the integrity of cell adhesion molecules like Ninj1 is crucial for homeostasis. In Ninj1 knockout mice (which are genetically manipulated to lack this cell adhesion molecule), behavior is altered when compared to mice that do not have this gene missing. Ninj1 knockout mice exhibit anxiety and high instances of repetitive behaviors which include increased levels of self-grooming behaviors. While Ninj1 mice have increased levels of ionotropic glutamate receptors, they also have reduced levels of glutamate, thus exhibiting glutamatergic abnormalities as well.
• SAPAP3-mutant mice. The SAP90/PSD95-associated protein 3 (SAPAP3 is sometimes also referred to as DLGAP3 in scientific literature) is a scaffolding protein found in excitatory postsynapses and is highly expressed in the striatum, a part of the brain that is involved in automating movement. SAPAP3-mutant mice have this scaffolding protein genetically deleted and are frequently used in animal research for the purposes of modeling obsessive-compulsive disorder (OCD), an anxiety-spectrum disorder which is defined by unwanted persistent thoughts (referred to as ‘obsessions’) and repetitive actions (known as ‘compulsions’). SAPAP3-mutant mice have defects in their cortico-striatal synapses and a behavioral profile which reflects OCD-like behaviors, such as increased anxiety combined with elevated self-grooming behavior which persists in many cases until the mouse develops skin lesions and facial hair loss.
• BTBR mice. BTBR T+tf/J (BTBR) mice are typically used for modeling autism spectrum disorders in mice since their behaviors are consistent with the three diagnostic criteria for autism spectrum disorders. This inbred mouse strain was first developed at Columbia University by crossing mice which carried the wildtype T (brachyury) gene with mice that carried the tufted (tf) mutation. BTBR mice also have brain malformations, inclusive abnormalities of the corpus callosum and a significant reduction in volume of the hippocampal commissure. As mentioned previously, BTBR mice are characterized by abnormal behaviors, including impaired communication and social interaction, as well as increased levels of repetitive behaviors including higher bouts of self-grooming. In an experimental setting, when BTBR mice are placed in an environment supporting free social interaction they demonstrate lower levels of allogrooming and play behavior and high levels of self-grooming.
• BALB/C mice. BALB/C mice are commonly used in animal research. They are characterized by their sociability deficits and are used to model autism spectrum disorders, but can also be used to model other neurological diseases and tumors as well. Even though BALB/C mice are used to characterize autism, they demonstrate low self-grooming levels. This stands in contrast to other mouse models of autism which display high levels of repetitive self-grooming.
• SHANK3 mice. SHANK3 is a postsynaptic protein found at glutamatergic synapses and is involved in establishing normal development of connectivity in the brain. In general, proteins which belong to the Shank family are thought to work as scaffolding proteins which help orchestrate the postsynaptic signaling complex of glutamatergic synapses. Disruption of the Shank3 gene is believed to be the major cause of the 22q13 deletion syndrome (also known as the Pheland-McDermid syndrome) which is an autism spectrum disorder. Shank3 mutant mice are used to study the relationship between this gene, behavior, and autism spectrum disorder. Shank3 mutant mice exhibit repetitive self-grooming to the point it becomes a self-injurious behavior.
• R6/2 mice. R6/2 mice are transgenic mice used for modeling Huntington’s disease in animal research studies. R6/2 mice express exon 1 of the human Huntington’s disease gene with about 150 CAG trinucleotide repeats (i.e., the repetition of cytosine, adenine, and guanine). In R6/2 mice, the human huntingtin promoter drives the transgene expression which results in a 75% endogenous huntingtin expression. From all Huntington’s disease mouse models to date, R6/2 develop this disease the fastest and have the highest expressions of the huntingtin protein across different levels of the brain. These mice also show elevated levels of self-grooming, resembling stereotypy, combined with other changes in motor function, including altered gait patterns and involuntary movements.
• Hdh^Q111/Q111 mice. Hdh^Q111/Q111mice are used to model Huntington’s disease since they carry an expanded polyglutamine stretch in the protein that is associated with Huntington’s disease. But, unlike other models, Hdh^Q111 mice show only a mild phenotype combined with a relatively slow disease progression. Furthermore, these mice demonstrate changes in locomotor function as well as an anxio-depressive-like phenotype. In females, decreased grooming duration is observed, indicating that this mouse strain exhibits a sex and genotype interaction. In this context, female mice which exhibit decreased grooming behaviors are interpreted as being in a depressive-live state which is not observed in male same-strain mice (which are more likely to demonstrate an anxiety-like phenotype).
• Slitrk5 mice. Slitrk5 is a neuron-specific transmembrane protein whose function is still unknown. However, mice that have the gene for Slitrk5 knocked out have alterations in their self-grooming pattern which is similar to the pathological grooming (combined with anxiety) that can be observed in SAPAP3 mice (which were discussed earlier). Slitrk5 mice demonstrate reduced neuronal transmission at corticostriatal synapses and reduced levels of the corticostriatal synapses NR1 and NR2B. Although Slitrk5 mice are used experimentally to model obsessive-compulsive disorder, genetic evidence which links the Slitrk5 gene with obsessive-compulsive disorder in humans is yet to be established.

Abnormalities of Grooming Behaviors

Allogrooming Abnormalities

• Autism spectrum disorder. Since allogrooming is an affiliative behavior, the presence of autism spectrum disorder leads to abnormalities in allogrooming due to the social deficits associated with the neuropsychiatric condition. Mice which model autism spectrum disorder, be they genetic models such as the BTBR strain or chemically induced, are likely to have low instances of allogrooming and high instances of self-grooming.

Cephalocaudal Grooming Abnormalities

• Lack of vitamin D receptor. The sequential pattern that constitutes cephalocaudal grooming (paw licking, nose/face washing, body washing, and tail/genital washing) is disrupted in mice which lack the vitamin D receptor gene.
• Chronic stress. Chronic stress is a variable that is known to cause an abnormal manifestation of cephalocaudal grooming. Prolonged periods of stress will alter a mouse’s cephalocaudal grooming sequence and create disorganized patterning in their grooming response.

Self-Grooming Abnormalities

• Autism. Autism spectrum disorders are typically characterized by a similar neuropsychological deficits profile which includes limited social interactions, reduced communication, and repetitive behaviors. ASDs affect many children, people, and families and receive a lot of research attention including from scientists who make use of animal models. Autism-like features are observed in mouse strains such as BTBR and SHANK3 mice. These two strains demonstrate increased frequency of self-grooming in combination with autism-specific deficiencies such as lack of social interaction.
• Huntington’s disease. Huntington’s disease is an autosomal dominant disorder. It occurs due to the expression of the huntingtin protein which expands and forms an abnormal protein, ultimately damaging brain cells. In mice modeling Huntington’s disease, altered levels of self-grooming can be observed when compared to wild-type controls. For example, by the time that R6/2 mice (the most commonly used mouse strain for modeling Huntington’s disease) reach 13 weeks of age, they will spend twice the time grooming when compared to wild-type controls.
• Prion disease. Prion disease can be acquired through exposure, spontaneously, or genetically. It is a disease characterized by the misfolding of the prion protein (a protein whose function is still not completely understood by scientists) which ultimately leads to dementia, severe ataxia, and even death. In animal research, the most common way to induce prion disease in mice is by infecting wild type mice with certain strains of prion. After being inoculated with prion disease for about 5.5 months, mice will begin to show decreased levels of self-grooming behavior when compared to uninoculated controls. However, even though mice with prion disease show decreased levels of self-grooming, they show hyperactivity in terms of locomotion.

Disease Models of Grooming Behaviors

Allogrooming Disease Models

• Autism spectrum disorders mouse disease models and allogrooming.
  • EN2 -/- mice model ASD and have altered allogrooming behaviors. In genetics research, the homeobox transcription factory (EN2) has been shown in human studies to be correlated with ASD susceptibility. So, researchers are using EN2 -/- mice which lack EN2, in order to model ASD. One study showed that EN2 -/- mice had less instances of allogrooming when compared with the control group. Since allogrooming is a social behavior, this finding was interpreted to parallel the social deficits observed in humans with ASD. On a side note, the researchers also found that the ASD mice had difficulty in memory tasks, as shown from the data acquired by means of using the Morris Water Maze and the increased latency times in each test trial, possibly implying a relationship between grooming, sociability, and memory abilities.
  • BTBR mice model ASD and have altered allogrooming behaviors. BTBR T+tf/J (BTBR) mice demonstrate low levels of allogrooming, which is in line with their general low-sociability behavioral phenotype. BTBR mice are an inbred mouse strain which are commonly used in behavioral studies for the purposes of modeling the diagnostic symptoms associated with autism.
  • R1117X mutant mice model ASD and have altered allogrooming behaviors. The SHANK3 gene is implicated in having many different functions in the brain due to its structure complexity and thus is an important gene for optimum performance. SHANK3 abnormalities have also been identified in patients with autism spectrum disorder.
  • XAV939 injections lead to ASD mouse model induction. As mentioned previously, under the ‘Pharmaceutical’ section, XAV939 injections will have increased levels of self-grooming but decreased allogrooming.
  • Valproic acid leads to ASD mouse model induction. The mechanisms and relationship between valproic acid and ASD induction was explained under the ‘Pharmaceutical’ section. But, valproic acid is another method for inducing ASD in mice.

Barbering Disease Models

• NOS2 knockout mice serve as a trichotillomania mouse model. NOS2 knockout mice model trichotillomania and demonstrate high levels of barbering. Trichotillomania is an impulse control disorder which is commonly studied in behavioral research since it is estimated to affect 1-3.5% of the human population. Trichotillomania is characterized by the urge for hair trimming or pulling and can be modeled in mice either through genetic induction or spontaneously. If you’d like to learn more about the trichotillomania mouse models, check out our barbering article.

Cephalocaudal Grooming Disease Models

• Mouse Hoxb8 mutants model trichotillomania. When cephalocaudal grooming is on endless repeat, mice are essentially exhibiting excessive grooming and inevitably remove their hair and fur. Such is the case with mouse Hoxb8 mutants which show excessive grooming patterns. Interestingly, when these mice are given a bone marrow transplant from wild-type mice, their pathological phenotype is rescued.
• BTBR T+tf/J mouse model of autism. The BTBR T+tf/J mouse model of autism displays a high frequency of cephalocaudal grooming in which the grooming pattern is repeated quickly. This model is further characterized by an increased frequency of interrupted bouts, meaning that the mouse can suddenly pause in between grooming stages before continuing to the next area of grooming.

Self-Grooming Disease Models

• Autism disease models. Self-grooming is a variable of interest to behavioral scientists studying ASDs since it has an inverse relationship with other social behaviors. In other words, as instances of self-grooming increase, a decrease in other social behaviors is likely to be observed. Therefore, self-grooming is a behavior that is of interest to behavioral scientists interested in understanding and potentially treating ASDs.
  • Mice such as BTBR, SHANK3, and SAPAP3-mutant mice, as mentioned previously, may be used for the purposes of studying self-grooming in ASDs.
  • ASDs can also be chemically induced in mice via injections of valproic acid, as mentioned previously. Mice that have been exposed to valproic acid also display behaviors that are analogous to those seen in humans with ASDs, including increased repetitive behaviors (seen as increased self-grooming in mice) and decreased social interactions.
• Huntington’s disease models. As mentioned previously, Huntington’s disease models show altered levels of self-grooming. R6/2 transgenic mice and Hdh^Q111 mice are two commonly used mouse strains for studying Huntington’s disease in mice. While R6/2 mice show an increase of stereotypic self-grooming, Hdh^Q111 mice (especially females) demonstrate a decrease in self-grooming behaviors which is associated with a depressive-like phenotype.
• Obsessive-compulsive disorder. Since self-grooming already takes up such a large proportion (about 40%) of a mouse’s waking time, any increase of its frequency is bound to be problematic. OCD models of self-grooming are associated with higher levels of self-grooming which, in some cases, even becomes self-injurious.
  • Genetic mouse modeling is the most commonly used method for studying OCD in mice. The SAPAP3 and slitrk5 mouse strains are used frequently in scientific research for the purposes of studying repetitive behaviors like self-grooming within an OCD model.

Summary

• Grooming refers to the cleaning that a mouse does on its (or another mouse’s) fur and body. 
• Grooming behaviors are typically classified as maintenance behavior. 
• Grooming is also an active behavior and, in some cases, grooming may also be an abnormal behavior, an agonistic behavior, or a sexual behavior. 
• Nibbling, scratching, licking, and biting are behaviors that are related to the grooming behaviors.
• There are many types of grooming behaviors, including: allogrooming, barbering, cephalocaudal grooming, post-copulatory grooming, scratching, self-grooming, and ulcerative dermatitis. 
• Depending on the grooming behavior, there are different types of functions that are involved. Generally, the functions of grooming behavior are to: decrease pain, maintain thermoregulation, maintain body care. 
• Behavioral studies, pharmaceutical studies, and genetic studies are all commonly used research techniques for studying grooming behaviors. 
• Commonly used behavioral tests for assessing grooming behaviors include: adhesive tape removal test, social interaction test, three-chamber test, the spray test, visible burrow system, open field test, elevated plus-maze, tube dominance test, and the resident-intruder test. 
• Some notable pharmaceutical studies on grooming behaviors have established that
  • for allogrooming:
    • stadium valproate decreases allogrooming
    • XAV939 injections decrease allogrooming
    • oxytocin antagonist may increase vigorous allogrooming
    • L-DOPA combined with social defeat experience can decrease allogrooming
  • for barbering: 
    • lomipramine reduces barbering in trichotillomania mice 
    • estradiol injections also reduce barbering in mice modeling trichotillomania. 
  • for cephalocaudal grooming 
    • diazepam enhances cephalocaudal grooming
    • pentylenetetrazole also affects cephalocaudal grooming
    • fluoxetine decreases it
    • amitriptyline also decreases cephalocaudal grooming. 
  • for self-grooming
    • XAV939 and valproic acid are each individually able to increase self-grooming
    • fluoxetine and MPEP are able to reduce self-grooming behavior. 
• Across mouse strains, grooming behaviors are differently exhibited. For example:
  • for allogrooming
    • BTBR, NF-κB p-50 deficient, and EN2-/- have low levels of allogrooming
    • R117X mutant mice have increased levels of allogrooming
    • C57B1/6J, BALB/CJ, and NIH mice are all highly likely to display subordinate allogrooming behavior. 
  • for barbering
    • NMRI mice serve as a comparator strain, as do C57BL/6 mice.
    • 129S1 female mice are more likely to exhibit barbering than male mice under certain conditions.
    • BALB mice may also have gender differences when it comes to barbering
    • PLCβ1^-/- mice have low instances of barbering and other social behaviors
    • A2G mice demonstrate dominance barbering. 
    • NOS2 knockout mice demonstrate high levels of barbering behaviors.
    • GalNAc-4-ST1-/- mice have very high levels of barbering amongst one another. 
    • S-COMT deficient mice show increased barbering behavior and other subtle changes in social interaction behaviors. 
  • for cephalocaudal grooming
    • 129S1 mice demonstrate low grooming activity
    • BALB/c and NMRI mice display normal cephalocaudal grooming patterns.
  • for self-grooming 
    • Ninj1 knockout mice have high levels of self-grooming.
    • SAPAP3-mutant mice have elevated self-grooming levels.
    • BTBR mice have increased levels of self-grooming and other repetitive behaviors.
    • BALB/C mice also have high levels of repetitive self-grooming
    • SHANK3 mice demonstrate self-grooming to the point it becomes a self-injurious behavior. 
    • R6/2 mice show elevated levels of self-grooming combined with other changes in motor function.
    • Slitrk5 mice have an abnormal grooming pattern, similar to that of SAPAP3 mice. 
• Abnormalities largely affect grooming behaviors, for example:
  • allogrooming can be displayed in higher or lower instances than normal due to autism spectrum disorder. 
  • for cephalocaudal grooming
    • lack of vitamin D receptors is associated with disrupted grooming sequence
    • chronic stress will also disorganize the innate grooming pattern that mice follow
  • for self-grooming
    • autism will also increase or decrease self-grooming manifestation
    • huntington’s disease will also lead to altered self-grooming profiles
    • prion disease is another abnormality that affects self-grooming behavior in mice.
• Disease models can be used to model abnormalities or diseases of self-grooming in mice. 
  • For allogrooming, the following ASD mouse models exist:
    • EN2-/- mice 
    • BTBR mice 
    • R1117X mutant mice 
    • XAV939 injections
    • Valproic acid
  • For barbering, the following mouse models exist:
    • Mouse Hoxb8 mutants model trichotillomania
    • BTBR mice model ASDs
  • For self-grooming, the following mouse disease models show altered behaviors:
    • For ASDs, BTBR, SHANK3, and SAPAP3-mutant mice have altered self-grooming profiles. 
    • Furthermore, self-grooming ASDs disease models can be induced by valproic acid. hoxb8 mutants model trichotillomania and the subsequent behavioral changes
    • For Huntington’s disease, specific mouse strains such as R6/2 mice will model it.
    • OCD models can be modeled by specific mouse strains as well, such as the SAPAP3 and slitrk5 mouse strains. 

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