B6By.Cg-Kit^W-v Mitf^Mi-wh T/J

Stock number: 000350
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

This congenic strain carries three mutant alleles (Kit^W-v Mitf^Mi-wh T) affecting pigmentation and various cellular or developmental defects.

Detailed description

Kit mice possess pleiotropic defects in pigment-forming cells, germ cells, RBC's and mast cells. In addition, they exhibit impaired resistance to parasitic infection and an intrinsic progenitor cell defect. Kit^W-v homozygotes resemble Kit^W homozygotes in color, anemia, and germ cells, but many of them survive to maturity. The lack of germ cells in mutant mice leads to the development of some ovarian tumors (mesotheliomas and granulosa cell), associated with an overproduction of pituitary gonadotropic hormone. 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 heterozygous for the brachyury spontaneous mutation (T) have tail defects and associated skeletal abnormalities.

Development

The Kit^W-v mutation arose spontaneously at The Jackson Laboratory in strain C57BL/6J before 1937. The mutation Mitf^Mi-wh arose spontaneously in offspring of a cross between strains DBA and C57BL at the University of Rochester about 1947. T was found by Dobrovolskaia-Zavadskaia in a laboratory stock about 1927. Both Mitf^Mi-wh and T were imported into The Jackson Laboratory from Dr. D. Falconer of Edinburgh in 1950. Both mutations were together in a dominant testing stock that had been outcrossed to CBA and C57. At The Jackson Laboratory they were maintained together by sibling matings. In 1958 a Kit^W-v Mitf^Mi-wh T linkage testing stock was constructed. The stock was sibling bred and subsequently backcrossed to C57BL/6By. In 1981 Kit^W-v/+ Mitf^Mi-wh/+ T/+ males at N29F2 were bred with C57BL/6By females to generate embryos for cryopreservation.

Allele

Symbol: T
Name: brachyury
MGI accession ID: MGI:1856184
Generation method: Spontaneous
Synonyms: T1
Marker symbol: T
Marker name: brachyury, T-box transcription factor T
Marker synonyms: Bra; SAVA; T1; Tbxt; TFT
Chromosome: 17
Strain of origin: Laboratory stock
Molecular note: Pulsed-field gel electrophoresis revealed an altered restriction fragment size consistent with a deletion of 160-200kb.

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: Kit^W-v
Name: viable dominant spotting
MGI accession ID: MGI:1856266
Generation method: Spontaneous
Synonyms: Kit^Wv; W^'; W²; W^v; Wv
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Marker synonyms: belly-spot; CD117; c-KIT; Dominant white spotting; Gsfsco1; Gsfsco5; Gsfsow3; MASTC; PBT; SCFR; SCO1; SCO5; SOW3; Steel Factor Receptor; Tr-kit
Chromosome: 5
Strain of origin: silvered black strain
Molecular note: A C-to-T point mutation at coding nucleotide 1979 (transcript NM_021099) results in a threonine to methionine substitution at amino acid 660 (p.T660M).