B6.C(Cg)-Atcay^ji/BurJ

Stock number: 008140
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Mice homozygous for the spontaneous mutation, jittery (ji) in Atcay (ataxia, cerebellar, Cayman type homolog), exhibit severe, progressive ataxia and die at approximately 4 weeks of age. This mutant mouse strain represents a model that may be useful in studies of congenital ataxia.

Detailed description

ji homozygotes can first be identified at approximately 12 days of age by a leaning, zig-zag gait when they attempt to run and by the difficulty they have righting themselves when placed on their backs. Disease progression is rapid such that within two more days mutants are found to crouch on their heels in a squatting position and can not run without falling. Within three to four days of the first symptoms, tetany is seen during exertion or excitement. This is initially most pronounced in the forelegs, which the mice beat up and down during these two- to three-second spasms. Failure to gain weight is seen by the third week of life and it is unclear whether this results from an inability to take in food. The severity and frequency of tetany increases, and during the fourth week weight loss and increased weakness precede death. The mean age of death is approximately 31 days. Tetrahydrobiopterin levels in the brain and GTP cyclohydrolase activity in the liver are lower in ji homozygotes than normal. At 20 days of age, serum calcium is within normal ranges. Parabiotic twins made with an affected and an unaffected sibling do not transfer a mutant phenotype to the normal partner indicating that a diffusible factor does not cause the mutant phenotype. However, tetany and weight loss are inhibited in the mutant partner which also has increased longevity, yet still develops failed muscle coordination and a crouching posture. (DeOme, 1945; Snell, 1950; Duch et al., 1986.)
The donating investigator reports that the phenotype observed on the C57BL/6J background is similar to the original JIGR background (unpublished).

Development

Jittery (Atcay^ji) arose as a spontaneous mutation in BALB/c, the Bagg albino strain, before 1945. It was segregating in the waltzer stock (see V/Le, Stock No. 000275) that Dr. Ludwin sent to Dr. Snell at the Jackson Laboratory in 1947. Jittery remained segregating in the waltzer stock until 1959 when a jittery (ji/ji) male was outcrossed to a C57BL10 female. Following this cross sibling matings were used until F15 in 1964 when a ji/ji male was mated to an inbred grizzled (gr/gr) female at F30. Because ji and gr were closely linked on chromosome 10 a balanced cross with the two loci in repulsion was used to create the inbred JIGR strain (Stock No. 000572). Subsequently, Dr. Margit Burmeister at the University of Michigan outcrossed JIGR/DnJ to C57BL/6J and selected for ji. Backcrossing reached 15 generations in 2007. The strain was donated to the Repository in 2007.

Allele

Symbol: Atcay^ji
Name: jittery
MGI accession ID: MGI:1856574
Generation method: Spontaneous
Marker symbol: Atcay
Marker name: ataxia, cerebellar, Cayman type
Chromosome: 10
Strain of origin: BALB
Molecular note: The mutation in the jittery mouse has been identified as a B1 element insertion in exon 4 and results in a predicted protein of only 62 endogenous residues plus 21 missense residues.