STOCK a/a Mitf^Mi-wh +/+ Itpr1^opt/J

Stock number: 000302
Research areas: Dermatology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

This stock carries two spontaneous mutations, Mitf^Mi-wh (white) and Itpr1^opt (opisthotonus), that affect eye and coat pigmentation, and body movement and balance respectively.

Detailed description

Mutations at the Mitf locus affect eye size, pigmentation, and the capacity for secondary bone resorption. Mice homozygous for the white allele (Mitf^Mi-wh) display an overall absence of pigment cells with the exception of the retina which expresses a few giving the eye a small amount of pigment. Homozygotes show slight microphthalmia but a normal skeleton. Heterozygotes (Mitf^Mi-wh/+) have a diluted coat color, light ears, a white belly spot, and in rare cases a dorsal spot. In addition, they display abnormalities of both the cochlear and vestibular portions of the inner ear. Mice homozygous for the opisthotonus spontaneous mutation (Itpr1^opt) display a characteristic upward arching of head and tail. Homozygous mutant mice can be recognized at about 10 days of age by their loss of balance when standing or moving. Typical behavior of 15 to 20 day old homozygotes consists of falling over and struggling to get up. Agitation and severe opisthotonus ensue with death occuring by weaning age or before.

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; 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: Itpr1^opt
Name: opisthotonus
MGI accession ID: MGI:1856981
Generation method: Spontaneous
Synonyms: Itpr-1^opt
Marker symbol: Itpr1
Marker name: inositol 1,4,5-trisphosphate receptor 1
Marker synonyms: ACV; CLA4; I145TR; InsP3R; InsP3R type I; INSP3R1; IP3R; IP3R1; Itpr-1; opt; P400; Pcp1; Pcp-1; PPP1R94; SCA15; SCA16; SCA29; wblo
Chromosome: 6
Strain of origin: C57BLKS-Lepr^db-2J
Molecular note: The molecular defect underlying the phenotype in the opisthotonus mouse involves a genomic deletion that alters the Itpr1 protein. The genomic deletion removes the first two exons from the mRNA, but does not disrupt the translational reading frame. The protein is reduced in expression and is predicted to have lost several modulatory sites.

Allele

Symbol: Mitf^Mi-wh
Name: white
MGI accession ID: MGI:1856088
Generation method: Spontaneous
Synonyms: Mi^wh; mitf^wh
Marker symbol: Mitf
Marker name: melanogenesis associated transcription factor
Marker synonyms: BCC2; bHLHe32; CMM8; COMMAD; Gsfbcc2; MI; MITF-A; wh; WS2; WS2A
Chromosome: 6
Strain of origin: (C57BL x DBA)F1
Molecular note: T-to-A transversion at bp 764, which leads to an isoleucine to asparagine substitution at amino acid 212 in the encoded protein (p.I212N). This mutation is in the basic region of the protein.
General note: Combination heterozygotes of Mitf^Mi-wh/Mitf^Mi, Mitf^Mi-wh/Mitf^Mi-b, and Mitf^Mi-wh/Mitf^Mi-ws show some interallelic complementation in that the heterozygote of the two alleles is more nearly normal than either homozygote (J:12967, J:19656). Mitf^Mi-b/Mitf^Mi-wh agouti mice are light cream with white spots and ruby eyes (J:15061).