STOCK Mitf^Mi-wh +/+ Wnt7a^px/J

Stock number: 001253
Research areas: Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Sensorineural Research

Description

Individual mice of this stock recovered from cryopreservation will carry one of the two mutant alleles, Mitf^Mi-wh or Wnt7a^px. Heterozygous Mitf^Mi-wh mice 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.

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 abnormalitites of both the cochlear and vestibular portions of the inner ear. Mice homozygous for the postaxial hemimelia spontaneous mutation (Wnt7a^px) have skeletal defects of the forelimbs. Digits 5, 4, and sometimes 3, are missing and there is a reduction or absence of the ulna. There is always a large oval foramen in the scapula. The hindlimbs are usually unaffected, but digit 5 may be absent, and occasionally the fibula is reduced. Severely affected mice tend to have an extra pair of ribs and a slight reduction in the number of presacral vertebrae. Both sexes are sterile and show anomalies of the Mullerian ducts.

Development

The mutation postaxial hemimelia was identified in the first female expressing the ragged mutation, which arose in a translocation stock and was identified by Carter & Phillips in approximately 1954. A. G. Searle first described the postaxial hemimelia mutation in 1963 and in 1986 carriers were sent from Harwell to The Jackson Laboratory. The imported mutant was maintained in repulsion with Mitf^Mi-wh. In 1987 embryos were generated for cryopreservation by crossing C57BL/6J females with Mitf^Mi-wh +/+ Wnt7a^px males.

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).

Allele

Symbol: Wnt7a^px
Name: postaxial hemimelia
MGI accession ID: MGI:1857009
Generation method: Spontaneous
Synonyms: px
Marker symbol: Wnt7a
Marker name: wingless-type MMTV integration site family, member 7A
Marker synonyms: SANTOS; tw; Wnt-7a
Chromosome: 6
Strain of origin: STOCK Sox18^Ra
Molecular note: A 515 bp deletion at the end of exon 3. This results in utilization of a cryptic splice site in exon 3. This alteration in the mRNA is predicted to create a shift in the reading frame and the introduction of a stop codon at the beginning of the fourth exon.