Although no overt phenotype is apparent in newborn hyh mice, they have dilated lateral ventricles. By 2 weeks of age, an outward phenotype of a domed head and a hop gait is apparent. Dissection and histological examination reveal "hydrocephalus of lateral and third ventricles and of the caudal aspects of the cerebral aqueduct" increasing in severity with age (Bronson et al., 1990). Homozygotes have a decreased lifespan usually dying before 2 months of age. Some homozygotes will live for several months, but usually will not breed.
The hyh mutation arose spontaneously on the C57BL/10J background in 1981 and was sibling mated by progeny tested heterozygote x heterozygote for 11 generations and was then outcrossed onto a B6C3Fe-a/a background. This strain is maintained by ovarian transplant-backcross-intercross using homozygous ovary donors whose hosts are bred with B6C3Fe-a/a F1 males and the obligate heterozygous offspring are then sibling bred, generating homozygous female ovary donors.
|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.|
|Allele Name||hydrocephaly with hop gait|
|Gene Symbol and Name||Napa, N-ethylmaleimide sensitive fusion protein attachment protein alpha|
|Strain of Origin||C57BL/10J|
|Molecular Note||The G-to-A transition identified in exon 4 results in the substitution of the conserved methionine at amino acid residue 105 with an isoleucine (p.M105I). Transcript expression levels were normal as determined by Northern blot analysis. Presence of the mutation was confirmed by RT-PCR sequence analysis of mRNA from brain tissue. Western blot analysis indicated that the mutant protein is about 40% less abundant in homozygous mutant mice than is the normal protein in wild-type mice.|