B6C3Fe a/a-Hgs^tn/J

Stock number: 000245
Research areas: Developmental Biology Research, Neurobiology Research

Detailed description

Mice homozygous for the teetering spontaneous mutation (tn) die between 5 and 6 weeks of age. Homozygous mutant mice are first recognizable at 25 to 30 days by their stiff, slow, unstable movements and their growth retardation. They may assume and maintain unusual postures. Occasionally they have running "fits". Just prior to death they look emaciated and lie on their sides with all limbs extended. In the brainstem and spinal cord there is dysgenesis of selective regions including the pons, trapezoid body, olivary and fastigial nuclei, and the pyramidal tract. There is also progressive Purkinje cell loss. Positional cloning reveals that the teetering, tn, mutation is a single nucleotide substitution (adenine to guanine transition at position 265, M89V)in the Hgs, HGF-regulated tyrosine kinase substrate, gene.

Development

The teetering mutation spontaneously arose in the C3H/HeJ inbred strain in 1959 at The Jackson Laboratory. The mutation was backcrossed to C57BL/6J six times and maintained as a sibling mating. In 1979, a high incidence of hydrocephalus in the colony prompted an outcross to B6C3FeF1/J a/a. This strain was cryopreserved as embryos in 1986.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; Asip; ASP; SHEP9
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
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 a^t-2Gso and A^w-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.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039

Allele

Symbol: Hgs^tn
Name: teetering
MGI accession ID: MGI:1857076
Generation method: Spontaneous
Attributes: Hypomorph
Marker symbol: Hgs
Marker name: HGF-regulated tyrosine kinase substrate
Marker synonyms: HRS; tn
Chromosome: 11
Strain of origin: C3H/HeJ
Molecular note: A spontaneous A-to-G point mutation results in the amino acid substitution of methionine with valine at position 89 (p.M89V).