This strain carries two spontaneous mutations in repulsion, jittery (Atcayji) and grizzled (Mfsd12gr). Jittery mice are characterized by muscular incoordination and seizures. Grizzled mice are characterized by a coat color resembling chinchilla and small size.Read More +
This strain carries gr and Atcayji in repulsion.
JIGR/Dn is maintained with jittery (Atcayji) and grizzled (Mfsd12gr) in repulsion.
Atcayji 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 Atcayji 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.)
Mfsd12gr is a recessive mutation that occasionally causes tail kinks and consistently causes dilution of the yellow pigment but not the black pigment of the hair. The coat color has been described as similar to chinchilla (Tyrc-ch/Tyrc-ch) but with the black pigment remaining undiluted. On the agouti JIGR/Dn background the Mfsd12gr/Mfsd12gr coat color is grayish agouti. On a non-agouti background the hair in the ears and around the genitalia is white. The Mfsd12gr mutation causes 40-50% mortality prior to phenotypic classification and this affects males more than females. This mortality is both postnatal and prenatal from approximately 10 days onward. Pregnant dams expected to carry some homozygotes have been found to carry some dead embryos some of which had craneofacial abnormalities including shortened snout and swollen optic and occipital regions. At birth homozygotes weigh an average of one quarter less than their wildtype siblings. Although they increase in weight as suckling pups, as adults they still weigh 5-25% less than their wild type siblings. (Falconer, 1950; Bloom and Falconer, 1966.)
Jittery (Atcayji) 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 (Atcayji/Atcayji) male was outcrossed to a C57BL10 female. Following this cross sibling matings were used until F15 in 1964 when a Atcayji/Atcayji male was mated to an inbred grizzled (Mfsd12gr/Mfsd12gr) female at F30. Grizzled had appeared in descendants of mice from a cross of strain A at Edinburgh and a fuzzy stock from Cambridge. The Jackson Laboratory received grizzled from Dr. D. Falconer at Edinburgh in 1950. It had been crossed twice to CBA and was then sister x brother bred by Snell using forced heterozygosis. Because Atcayji and Mfsd12gr were closely linked on Chromosome 10 a balanced cross with the two loci in repulsion was used to maintain the JIGR strain. It was inbred and cryopreserved in 1987 by mating presumed Atcayji +/+ Mfsd12gr males and females at F74.
|Allele Type||Spontaneous (Null/Knockout)|
|Gene Symbol and Name||Mfsd12, major facilitator superfamily domain containing 12|
|Strain of Origin||A x STOCK-Sgk3fz|
|Molecular Note||A spontaneous mutation deletes 9 base pairs in-frame within exon 2.|
|Gene Symbol and Name||Atcay, ataxia, cerebellar, Cayman type|
|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.|
JIGR/Dn is maintained with jittery (Atcayji) and grizzled (gr) in repulsion. Homozygous gr have reduced viability and homozygous ji die between 17 and 20 days of age. Breeding is performed by mating repulsion double heterozygotes, ji +/+ gr, which are expected to yield 25% jittery, 50% wild-type repulsion double heterozygotes for further breeding, and 25% grizzled. The risk of recombination is minimal.
When using the JIGR/DnJ mouse strain in a publication, please include JAX stock #000572 in your Materials and Methods section.
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