Overview
C3FeB6 A/Aw-J-Ankank/J, also known as progressive ankylosis, is a strain of mutant mouse that exhibits a joint disease resulting in severe mobility deficits.
History
The original mutation conferring progressive ankylosis appeared spontaneously in a mouse of the strain JGBF/Le. A female JGBF/Le was seen to display an unusual gait, and was subsequently crossed in a two-stage process with C3FeB6 mice.
JGFB/Le mice homozygous for the mutant ank allele were first bred with C3FeB6F1, and then the resulting heterozygous progeny were inbred. All of this development occurred in the mid 1970s. The jg and bf alleles characteristic of the original JGBF/Le strain had been completely removed from the line by 1976.
Finally in 1987, breeding homozygotes at generation 32 with C3FeB6-A/Aw-J stock was used to “freeze” the ank allele, and produce the current form of this strain.[1]
Physical Characteristics
This strain possesses the allele white-bellied agouti (Aw-J), which leads it to have brown fur on the back and yellowish/whitish fur on its underside. Homozygotes are smaller overall than heterozygotes, and have reduced bone mass. Some C3FeB6 A/Aw-J-Ankank/J mice exhibit balanitis (inflammation of the glans penis), priapism (unusually sustained penile erections) and/or skin lesions on their paws.[1]
Behavioral Characteristics & Handling
Mutant mice of this strain can be distinguished from the wild type shortly after birth by their inability to grip in the horizontal grid test.[1] This strain is not suitable in general for tests involving a high degree of locomotion such as rotarod or forced swim, except as a negative control.
Given these mice have swollen joints and weak bones, researchers are advised to take extreme care when handling them in order to avoid excessive pain or damage resulting from pressure on their skeleton.
Health Characteristics
The major health characteristic of this strain is its disease phenotype progressive alkalosis, caused by a mutant allele of the gene encoding for the protein ANK. ANK is situated in the cell membrane and transports inorganic pyrophosphate to the outside of cells.[2] It plays a key role in bone formation, inhibiting the formation of osteoclasts.[3]
A point mutation (G to T substitution) in the ank gene in C3FeB6 A/Aw-J-Ankank/J changes a glutamine codon to a stop codon, truncating the ANK protein and rendering it non-functional. Bone mass in these mutant mice is lower, bone formation occurs at a slower rate, and there is decreased expression of bone marker genes.
As a consequence of this retarded bone development, joints become inflamed and filled with fluid. Hydroxyapatite deposition leads to calcification, hyperplasia and ankylosis. Mobility is severely affected, manifesting in a slow, “flat-footed” gait and a crouched posture.
The mice also show an immune deficiency, as evidenced by their reduced response to phytohemagglutinin, although they respond normally to bacterial lipopolysaccharide. Homozygotes generally do not live beyond five months. They are fertile however, but have small litters.[1]
Major Experimental Uses
These mice are mainly of interest in the study of arthritis and other disorders of the joints, as well as research into immune deficiency and immunology in general.
References
- 000200 – C3FeB6 A/A-Ank/J. 2019. 000200 – C3FeB6 A/A-Ank/J. [ONLINE] Available at: https://www.jax.org/strain/000200. [Accessed 19 April 2019].
- ANKH – Progressive ankylosis protein homolog – Homo sapiens (Human) – ANKH gene & protein. 2019. ANKH – Progressive ankylosis protein homolog – Homo sapiens (Human) – ANKH gene & protein. [ONLINE] Available at: https://www.uniprot.org/uniprot/Q9HCJ1. [Accessed 19 April 2019].
- Kim, H. J., Minashima, T., McCarthy, E. F., Winkles, J. A., & Kirsch, T. 2010. Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling. Journal of bone and mineral research. 25(8), 1771–1783.