nma arose spontaneously in 1985 on the CBA/J inbred strain at The Jackson Laboratory. From the age of 12 days, mice homozygous for nma are smaller than their normal littermates, weighing 50% less. They exhibit an abnormal gait, in which the hind legs extend past the front legs, and hind limb weakness that causes the mice to fall to the side. When sitting, nma/nma mice overextend their rear legs and prop themselves up in the shavings or against the cage wall. When picked up by the tail, homozygotes extend their rear legs briefly, then clasp their hind feet. They cannot orient themselves in water and spiral to the bottom of the tank. nma/nma mice survive only a few days past weaning, even with food and water made readily available. Heterozygotes appear normal behaviorally, histologically and biochemically.
Examination of serial sections through the entire brain revealed no abnormalities. The spinal cord motor neurons, spinal roots, ganglia and nerves were normally organized and myelinated. There was no muscular dystrophy or neurogenic atrophy of the skeletal muscle. Somatic organs appeared normal. Bone and muscle from the fore- and hindlimbs "showed no consistent abnormalities" and appeared normally innervated. X-ray analysis revealed normal hip joint structure, excluding hip abnormality as the reason for the hind limb overextension. ABR threshold analysis indicated that mice homozygous for nma have normal hearing at 18-21 days of age, and histological analysis of inner ears revealed no anomalies. Homozygotes exhibited significantly lower serum glucose and alanine aminotransferase (ALT) levels than normal littermates; blood urea nitrogen (BUN) did not differ. Heterozygote values were intermediate between those of the F1 parental strains, indicating that heterozygosity for nma has no effect on these parameters (Ward-Bailey et al. 2000).
The mutation neuromuscular ataxia (nma) arose spontaneously in strain CBA/J at generation F195 at The Jackson Laboratory in 1985. A carrier mouse was outcrossed to a B6C3Fe-a/a F1 and the F1 pairs were mated. It was continually backcrossed to the hybrid B6C3Fe-a/a by the cross-intercross method. It was cryopreserved in 1995 by mating heterozygotes at generation N22+.
|Gene Symbol and Name||a, nonagouti|
|Strain of Origin||old mutant of the mouse fancy|
|General Note||Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039|
|Molecular Note||Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.|