B6.Cg-Kit^W-sh/HNihrJaeBsmGlliJ

Stock number: 012861
Product name: sash
Strain synonyms: c-Kit^w-sh , cKit^w-sh
Research areas: Dermatology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools, Sensorineural Research

Description

A C57BL/6J congenic version of this strain made via SNP marker-assisted speed congenic protocol is available as Stock No. 030764 (all 140+ tested markers outside the Kit genomic region were C57BL/6J).

The spontaneous Kit^W-sh (or "sash") mutation affects melanoblast and mast cell survival, and may be useful in studying melanogenesis, hematopoiesis, gametogenesis and mast cell deficiency.

Detailed description

The Kit^W-sh (or "sash") mutation results in an embryonic deficit and eventual abolishment of mast cells soon after birth. There is also a deficit of melanocytes and interstitial cells in these mice. Reduced numbers of melanocytes results in some hearing impairment in homozygotes. The Kit^W-sh mutation is a inversion in regulatory elements upstream of the c-kit element.

Homozygous mice have white coat, black eyes, and some pigment around the ears. Heterozygotes have black coat with a white sash at the midline. Wildtype mice should have black coat (indistinguishable from C57BL/6J). Additionally, The Jackson Laboratory Stock Nos. 012861 and 030764 have historically/consistently exhibited longer white fur covering the body of homozygotes, while heterozygotes have longer white belt/sash fur but normal length black fur. For Stock No. 030764, the longer white fur coat is more prevalent in the 3-5 week age range, by 6 weeks the coat in the majority of homozygotes breeders starts to look smoothed out, and may proceed to become a more typical length over time. For Stock No. 012861, the longer white fur coat may persist throughout the life of the animal.

Heterozygous and homozygous mice are fertile and not anemic.

2012: Findings of altered immune responses as a result of mast cell deficit in these mice include:
   •   heightened susceptibility to vaccinia virus skin infection;
   •   earlier and more severe experimental autoimmune encephalomyelitis disease (a model of multiple sclerosis) with extensive demyelination and inflammation in the CNS;
   •   exacerbated dermatitis upon repeated oxazolone challenge when compared to their wild-type;
   •   Ultra violet exposure in these mice does not induce immune suppression, as it does in wild type mice;
   •   lower serum IgE levels compared with wildtype mice under steady-state conditions and after N. brasiliensis (hookworm) infection;
   •   failure to elicit histamine release or contractile responses in trachea isolated from ovalbumin sensitized mast cell-deficient mice;
   •   development of ~50% more adenomas than littermate controls and with tumors being ~33% larger in Kit^W-sh mice;
   •   increased resistance to bacterial lipopolysaccharide injection;
   •   failure of ovalbumin sensitization to elicit histamine release or contractile responses in trachea isolated from sensitized Kit^W-sh mice.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available. Also see Stock No. 030764 that has been backcrossed to C57BL/6J using a marker-assisted speed congenic protocol.

Development

The Kit^W-sh (or "sash") mutation arose spontaneously on a litter produced from a C3H/HeH x 101/H mating at the MRC Radiobiology Unit at Harwell (H) in the U. K. (Lyon and Glenister 1982 Genet Res 39:315). The founder female was identified by a white sash around her midsection. The Kit^W-sh mutation is an inversion spanning a 2.8 Mbp segment proximal to the Kit locus that disrupts 5' regulatory sequences. The Kit^W-sh strain was transferred to Dr. Karen Steel (Nihr) also at Harwell, then to Dr. Rudolf Jaenisch (Jae) at MIT, and then to Dr. Peter Besmer (Bsm) at Sloan Kettering. Prior to the transfer to Dr. Besmer, this strain was reported to be backcrossed at least ten times to C57BL/6. Prior to 2005, Dr. Besmer's lab distributed Kit^W-sh mice to different laboratories, including Dr. Stephen Galli (Glli) at Stanford University and also The Jackson Laboratory Repository as Stock No. 005051. The pedigree for Stock No. 012861 follows the mice sent to Dr. Galli. In Dr. Galli's laboratory, Kit^W-sh mutant males were backcrossed to inbred C57BL/6J females for 11 generations, and then heterozygous females and wildtype male littermates were sent to The Jackson Laboratory in 2010. Upon arrival, these animals were used to rederive the living colony. Kit^W-sh mutant males were bred to C57BL/6J inbred females (Stock No. 000664) for one generation (N11+N1), and then maintained by breeding heterozygous mice with wildtype mice from the colony. By 2014, we maintain this colony by breeding homozygous mice together.

Allele

Symbol: Kit^W-sh
Name: sash
MGI accession ID: MGI:1856265
Generation method: Spontaneous
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Chromosome: 5
Strain of origin: (C3H/HeH x 101/H)F1
Molecular note: The molecular mutation of this allele is an inversion located proximal to the Kit structural gene that disrupts 5' regulatory sequences. Transcripts were not detectable from this allele in cultured mast cells derived from homozygous mice. However, an analysis of embryonic expression revealed that ectopic expression of Kit occurred in homozygous mice and normal expression was ablated.