Cloning and structural analysis of the human c-kit gene.
Cloning and structural analysis of the human c-kit gene.
复制标题
DOI：
--
复制
发表时间：
1992-07
期刊：
影响因子：
8
通讯作者：
G. R. Vandenbark;C. Decastro;H. Taylor;S. Dew-Knight;R. Kaufman
中科院分区：
文献类型：
--
作者：
G. R. Vandenbark;C. Decastro;H. Taylor;S. Dew-Knight;R. Kaufman
最近小鼠White spots和Steel基因座分别被鉴定为编码c-kit受体及其配体的基因，揭示了该配体和受体在胚胎发生、黑色素形成和造血中的重要性。为了确定c-kit原癌基因是否与人类疾病有关，我们分离了7个重叠的lambda重组，使用胎儿脑cDNA，并对正常人类基因（KIT）进行了表征。最长的转录本是5230 bp，是选择性剪接的，包括21个外显子，跨越超过70kb的DNA。从外显子-内含子结构中，我们定位了一个替代剪接位点在外显子9的3'端。整体的c-kit基因结构与CSF-1R基因（c-fms）非常相似。这种相似性包括一个大的第一个内含子，包含翻译序列的外显子数量相同以及非常相似的外显子-内含子边界。使用脉冲场凝胶电泳，我们将KIT与血小板来源的生长因子受体A基因连接起来，两者都位于700 kb的BssHI片段上。这些数据将有助于研究KIT表达的控制，以及识别人类疾病中该基因的突变或表达改变的潜力。
The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human disease, we isolated seven overlapping lambda recombinants, using a fetal brain cDNA, and characterized the normal human gene (KIT). The longest mapped transcript is 5230 bp, is alternatively spliced and includes 21 exons that span more than 70 kb of DNA. From the exon-intron structure, we have localized an alternative splice site to the 3' end of exon 9. The overall c-kit gene structure closely resembles that found in the CSF-1R gene (c-fms). This similarity includes a large first intron, the same number of exons containing translated sequence and very similar exon-intron boundaries. Using pulsed-field gel electrophoresis, we have linked KIT to the platelet-derived growth factor receptor A gene, with both residing on a 700-kb BssHI fragment. These data will allow investigation into the control of KIT expression and the potential to identify mutations or altered expression of this gene in human disease.