B6.C3-Kit^W-44J/J

Stock number: 000122
Product name: dominant spotting 44 Jackson
Strain synonyms: W⁴⁴
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

These mice carry a spontaneous remutation at the Kit locus characterized by reduced fertility, normal blood parameters, and minimal white belly spotting.

Detailed description

Kit^W-44J heterozygotes have white-tipped feet and a white tail tip although the belly spot standardly found in Kit^W* mutations is very small in this mutant, sometimes restricted to only a few hairs. Homozygotes have a flecked pelt that is predominantly white, especially ventrally, with pigmented patches particularly at the lateral borders. The pigmentation fades with age yielding black-eyed white mice by approximately 9 months of age. While many Kit^W-44J homozygotes are viable, fertility is diminished. Homozygous females have greatly reduced fertility and gonads that are smaller in size with reduced activity. Homozygous males are sterile although spermatogenesis occurs. The Kit^W-44J allele does not produce anemia in either its heterozygous or homozygous state. The red blood cell count, white blood cell count, hematocrit, and mean cell volume are normal. However, bone marrow transplantation experiments reveal that the colony forming units in the bone marrow of Kit^W-44J homozygotes are much lower than normal despite the fact that the bone marrow has a normal cell count. While bone marrow transplantation from Kit^W-44J homozygotes can cure anemia in Kit^W/Kit^W-v hosts, it repopulates more slowly than does wild type bone marrow. Bone marrow from Kit^W-44J homozygotes also fails to repopulate the mast cells in the skin of Kit^W/Kit^W-v hosts. Wild type bone marrow transplanted into non-irradiated hosts out-competes the endogenous erythropoeisis in Kit^W-44J homozygotes but not in wild type hosts, further confirming a deficiency in erythropoeisis in these non-anemic mice. Mice doubly heterozygous for Kit^W-44J and Kit^W-39J are more mildly anemic than mice doubly heterozygous for Kit^W-39J and other second Kit^W* alleles. (Geissler et al., 1981; Geissler and Russell, 1983; Sawada et al., 1991.)

Development

The Kit^W-44J mutation arose spontaneously at the Jackson Laboratory on the C3H/HeJ background in the mid-1970s. It was backcrossed to C57BL/6J and in 1980 heterozygous males at N33 were bred with C57BL/6J females to produce embryos for cryopreservation. (Geissler et al., 1981 and 1988.)

Allele

Symbol: Kit^W-44J
Name: dominant spotting 44 Jackson
MGI accession ID: MGI:1856247
Generation method: Spontaneous
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Chromosome: 5
Strain of origin: C3H/HeJ
Molecular note: Southern hybridization analyses of genomic DNA using probes corresponding to two specific lengths of amino acids from c-kit suggests that this allele comprises a 4-5 kb insertion that disrupts c-kit. The level of c-kit mRNA in homozygotes is markedly reduced.