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 obtai...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展开更多
基金supported by the National Natural Science Foundation of China(NO.30670231)Public Service Project of Lab Animal Science(NO.2008F80005)SRF for ROCS,SEM
文摘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
