The spontaneous KitW-sh (or "sash") mutation affects melanoblast and mast cell survival, and may be useful in studying melanogenesis, hematopoiesis, gametogenesis and mast cell deficiency.
Also see Stock No. 030764 that is being backcrossed to C57BL/6J using a speed congenic protocol.
Stephen J Galli, Stanford University School of Medicine
KitW-sh mutant mice are available with different amounts of backcrossing onto the C57BL/6J genetic background: KitW-sh mutant mice from Stock No. 005051 were found to be only ~87% C57BL/6 genetic background. In comparison, KitW-sh mutant mice from Stock No. 012861 have been backcrossed at least ten additional generations with C57BL/6J inbred animals. Therefore, Stock No. 012861 mice are a fully congenic model for studying KitW-sh on a C57BL/6J genetic background.
The KitW-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 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 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 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.
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 is being backcrossed to C57BL/6J using a speed congenic protocol.
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. Prior to 2005, Dr. Besmer's lab distributed KitW-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, KitW-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. KitW-sh mutant males were bred to C57BL/6J inbred females (Stock No. 000664) for one generation (N11+N1), and thereafter maintained by breeding heterozygous mice with wildtype mice from the colony.
|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.|
When maintaining the live colony, heterozygous or homozygous mice may be bred together. Genotyping may be performed by coat color: homozygous mice have white coat, black eyes, and some pigment around the ears. Heterozygotes are black with a white sash at the midline.
When using the sash mouse strain in a publication, please cite the originating article(s) and include JAX stock #012861 in your Materials and Methods section.