B6.Cg-Mitf^Mi-wh/Mitf^Mi/J

Stock number: 000158
Research areas: Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

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 white mutant mice show slight microphthalmia but normal skeleton. Mice heterozygous for the microphthalmia (Mitf^Mi) mutation have less iris pigment than wildtype and often have white spotting on the belly, head, and tail. Homozygous mutant mice have small eyes and are devoid of pigment in the eyes, inner ear, and skin. Homozygotes are deaf at an early age. There is a decrease of mast cells in the spleen and gut. Most homozygotes die around weaning but some may live for several months. There is a deficiency of secondary bone resorption (osteopetrosis) and the incisors fail to erupt. Immunological defects include decreased macrophage chemotactic responses, impaired proliferative responses to B cell and T cell mitogens, diminished responses in vitro to T-dependent and T-independent antigens and reduced NK cell activity. Compound heterozygotes (Mitf^Mi-wh/Mitf^Mi) closely resemble white homozygotes (Mitf^Mi-wh/Mitf^Mi-wh) but their eyes are slightly more pigmented and not as small.

Development

The white spontaneous mutation (Mitf^Mi-wh) was found among offspring of a cross between the DBA and C57BL strains. The microphthalmia (Mitf^Mi) was found among descendants of an irradiated male.

Allele

Symbol: Mitf^Mi
Name: microphthalmia
MGI accession ID: MGI:1856085
Generation method: Other
Marker symbol: Mitf
Marker name: melanogenesis associated transcription factor
Chromosome: 6
Strain of origin: Not Specified
Molecular note: This mutation was identified during an irradiation experiment, but it is not known whether it was induced in the treated male or spontaneously arose in an untreated mate. RT-PCR analysis identified a 3 nucleotide deletion in the transcript that results in a loss of one of four conserved arginine residues in the basic domain of the encoded protein. This mutation is predicted to affect the ability of the protein to bind DNA.
General note: This mutation produces an osteopetrosis that resembles human osteopetrosis more than that produced by Ctsf^op. Mitf^Mi mutant mice have normal levels of M-CSF and its receptor. Osteoplasts are produced, but are unable to function normally in bone resorption (J:22788).

Combination heterozygotes of Mitf^Mi-wh/Mitf^Mi show some interallelic complementation in that the heterozygote of the two alleles is more nearly normal than either homozygote (J:12967). Mitf^Mi-Or/Mitf^Mi mice resemble homozygous Mitf^Mi-Or (J:15060).

Allele

Symbol: Mitf^Mi-wh
Name: white
MGI accession ID: MGI:1856088
Generation method: Spontaneous
Marker symbol: Mitf
Marker name: melanogenesis associated transcription factor
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).