THE DOMINANT-WHITE SPOTTING (W) LOCUS OF THE MOUSE ENCODES THE C-KIT PROTO-ONCOGENE
THE DOMINANT-WHITE SPOTTING (W) LOCUS OF THE MOUSE ENCODES THE C-KIT PROTO-ONCOGENE
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DOI：
10.1016/0092-8674(88)90020-7
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发表时间：
1988-10-07
期刊：
影响因子：
64.5
通讯作者：
HOUSMAN, DE
中科院分区：
文献类型：
--
作者：
GEISSLER, EN;RYAN, MA;HOUSMAN, DE
小鼠W位点的突变对胚胎发育和造血有多效性影响。该位点突变体的特征性表型，包括白色被毛、不育和贫血，可归因于干细胞群体在发育过程中迁移和/或增殖的失败。定位实验表明，c-kit原癌基因编码一种假定的酪氨酸激酶受体，是W位点的候选基因。我们在这里表明，c-kit基因在两个自发突变的W等位基因W44和Wx中被破坏。编码c-kit多肽240 - 342氨基酸的基因组DNA在W44中被破坏；编码342 - 791氨基酸的区域在Wx中被破坏。W44纯合子c-kit mRNA水平明显降低。这些结果有力地支持了c-kit为W位点基因产物的鉴定。
Mutations at the W locus in the mouse have pleiotroic effects on embryonic development and hematopoiesis. The characteristic phenotype of mutants at this locus, which includes white coat color, sterility, and anemia, can be attributed to the failure of stem cell populations to migrate and/or proliferate effectively during development. Mapping experiments suggest that the c-kit proto-oncogene, which encodes a putative tyrosine kinase recpetor, is a candidate for the W locus. We show here that the c-kit gene is disrupted in two spontaneous mutant W alleles, W44 and Wx. Genomic DNA that encodes amino acids 240 to 342 of the c-kit polypeptide is disrupted in W44; the region encoding amino acids 342 to 791 is disrupted in Wx. W44 homozygotes exhibit a marked reduction in levels of c-kit mRNA. These results strongly support the identification of c-kit as the gene product of the W locus.