Smith E A, Seldin M F, Martinez L, Watson M L, Choudhury G G, Lalley P A, Pierce J, Aaronson S, Barker J, Naylor S L
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4811-5. doi: 10.1073/pnas.88.11.4811.
The mouse W19H mutation is an x-ray-induced deletion of more than 2 centimorgans on chromosome 5 encompassing the white spotting mutation W (encoded by the Kit protooncogene), patch (Ph), and recessive lethal (l) loci. The platelet-derived growth factor receptor alpha gene (PDGFRA) like Kit encodes a transmembrane receptor tyrosine kinase. By using mouse-Chinese hamster somatic cell hybrids and haplotype analysis in interspecific backcross mice, mouse Pdgfra was mapped to chromosome 5 in tight linkage with Kit. Hybridization of a PDGFRA probe to DNAs from W19H/ + heterozygous mice and patch heterozygous mice, and their wild-type littermates, demonstrated deletion of Pdgfra. Pulsed-field gel electrophoresis indicated that Kit and Pdgfra are linked on a 630-kilobase Mlu I DNA fragment. Thus the W19H deletion removes at least two receptor tyrosine kinases and the results suggest Pdgfra as a candidate for the Ph locus.
小鼠W19H突变是由X射线诱导的5号染色体上超过2厘摩的缺失,该区域包含白斑突变W(由Kit原癌基因编码)、斑驳(Ph)和隐性致死(l)位点。血小板衍生生长因子受体α基因(PDGFRA)与Kit一样,编码一种跨膜受体酪氨酸激酶。通过使用小鼠-中国仓鼠体细胞杂种以及种间回交小鼠的单倍型分析,将小鼠Pdgfra定位到与Kit紧密连锁的5号染色体上。用PDGFRA探针与W19H / +杂合小鼠、斑驳杂合小鼠及其野生型同窝小鼠的DNA进行杂交,结果表明Pdgfra发生了缺失。脉冲场凝胶电泳表明,Kit和Pdgfra位于一个630千碱基的Mlu I DNA片段上。因此,W19H缺失至少去除了两个受体酪氨酸激酶,结果提示Pdgfra是斑驳位点的一个候选基因。