Homozygous lethality and heterozygous spotting due to a novel missense mutation in the mouse Kit gene

N-ethyl-N-nitrosourea （ENU） mutagenesis in mice can be used to study gene function in vivo and to establish genetic mouse models of human disease. In this study, a white spotted mouse （named Kit^W-1 Bao） was obtained by ENU-induced mutagenesis. Inheritance testing showed a single-gene dominant mutation and lethality in the Kit^W-1 Bao homozygous mice. The mutation was mapped to Chromosome 5 between markers DSMit356 and DSMit308. The region contains the Kit gene, whose mutations are known to lead to pigmentation defects in mice. Sequence analysis of the Kit cDNA from Kit^W-1 Bao heterozygotes revealed an A to T missense mutation resulting in an amino acid substitution of Asp （D） by Val （V） at amino acid position 849 within a highly conserved tyrosine kinase domain. The combined phenotype displayed by the Kit^W-1 Bao heterozygous and homozygous mutant mice demonstrates the critical function of the highly conserved aspartie acid residue at position 849 in the Kit gene product