B6C3Fe a/a-Mitf^Mi/J

Stock number: 001573
Product name: microphthalmia
Research areas: Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

These Mitf^Mi mutant mice are characterized by small eyes, and lack of pigment in the eyes, inner ear, and skin, and early deafness. White spotting on the belly, head, and tail are common.

Detailed description

Mutations at the Mitf locus affect eye size, pigmentation, and the capacity for secondary bone resorption. Mice heterozygous for the 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.

Development

The semi-dominant mutation microphthalmia (Mitf^Mi) was found among descendants of an irradiated male by Hertwig before 1942. It was sent to Dr. E.S. Russell at The Jackson Laboratory from Dr. Hans Gruneberg in 1961. It was maintained with the dominant allele Mitf^Mi-wh and crossed to C57BL/6J as Mitf^Mi-wh/Mitf^Mi each N generation until 1986 at N100. It was then backcrossed to C57BL/6J without Mitf^Mi-wh to N105. A cross was then made of a host female bearing a C57BL/6J-Mitf^Mi homozygous ovary to a C3HeB/FeJ-a/a male. The strain was then maintained by mating to the hybrid B6C3Fe-a/a each cross generation and mating the offspring each intercross generation.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
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: 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).