In 2010, The Jackson Laboratory performed a 126 single nucleotide polymorphism analysis on all pedigree lines of KitW-sh mice from Stock No. 005051. This revealed 14/126 markers that were homozygous C3H/He allele-type (two on Chr 5 [including the marker at 76.4 Mbp; closest to the Kit locus], three on Chr 6, one on Chr 8, two on Chr 12, two on Chr 13, one on Chr 15, two on Chr 16, one on Chr 18). Additionally, two markers were segregating for C57BL/6 and C3H/He allele-type (one on Chr 6, one on Chr 16). The amount of 101/H markers present (if any) was not determined. These data show Stock No. 005051 to be only ~87% C57BL/6-genetic background; and suggests it was not completely backcrossed to C57BL/6 prior to arrival in 2004. Therefore, we also offer a fully C57BL/6J-congenic KitW-sh model (Stock No. 030764) for studying KitW-sh on a C57BL/6J genetic background.
The 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 KitW-sh mutation is a inversion in regulatory elements upstream of the c-kit element. Homozygotes are white with black eyes and some pigment around the ears. Heterozygotes are black with a white sash at the midline. The mice are fertile and not anemic.
Recent 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 wild-type 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 KitW-sh mice;
• increased resistance to bacterial lipopolysaccharide injection;
• failure of ovalbumin sensitization to elicit histamine release or contractile responses in trachea isolated from sensitized KitW-sh mice.
The KitW-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 KitW-sh mutation is an inversion spanning a 2.8 Mbp segment proximal to the Kit locus that disrupts 5' regulatory sequences. The KitW-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. Dr. Besmer donated the strain to The Jackson Laboratory Repository in 2004 (as Stock No. 005051). Upon arrival, the colony was maintained by breeding KitW-sh mice together.
In 2010, a 126 SNP (single nucleotide polymorphism) panel analysis representing all pedigree lines was performed by The Jackson Laboratory Repository. This revealed 14/126 markers that were homozygous C3H/He allele-type (two on chromosome 5 [including the marker at 76.4 Mbp; closest to the Kit locus], three on chromosome 6, one on chromosome 8, two on chromosome 12, two on chromosome 13, one on chromosome 15, two on chromosome 16, and one on chromosome 18). Additionally, 2/126 markers were segregating between C57BL/6 and C3H/He allele-type (one on chromosome 6 and one on chromosome 16). The amount of 101/H markers still present (if any) was not determined. These data show the mice to be only ~87% C57BL/6-genetic background, and suggest the mice were not completely backcrossed to C57BL/6 prior to arrival at The Jackson Laboratory Repository in 2004.
|Allele Synonym(s)||c-Kitwsh; Sash; Wsh; Wsh; W-sh|
|Gene Symbol and Name||Kit, KIT proto-oncogene receptor tyrosine kinase|
|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.|
Homozygotes are fertile and produce normal litters.
When using the sash mouse strain in a publication, please cite the originating article(s) and include JAX stock #005051 in your Materials and Methods section.
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