STEEL-DICKIE MUTATION ENCODES A C-KIT LIGAND LACKING TRANSMEMBRANE AND CYTOPLASMIC DOMAINS
STEEL-DICKIE MUTATION ENCODES A C-KIT LIGAND LACKING TRANSMEMBRANE AND CYTOPLASMIC DOMAINS
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DOI：
10.1073/pnas.88.11.4671
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
COPELAND, NG
中科院分区：
文献类型：
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作者：
BRANNAN, CI;LYMAN, SD;COPELAND, NG
具有可存活的S1等位基因steel-Dickie（S1（d））的纯合子小鼠不育，严重贫血，黑眼白色。 在分子水平上研究了Sl（d）突变的性质，发现其是由于肥大细胞生长因子（MGF）基因组序列中的4.0-脱氢酶基因内缺失，提供了Sl编码MGF的确凿证据。 由于该缺失，Sl（d）仅能够编码缺乏跨膜和胞质结构域的可溶性截短生长因子。 北方分析表明，S1（d）mRNA在成体组织中以近似野生型水平表达，酵母表达研究表明，S1（d）蛋白与野生型可溶性MGF一样具有生物活性。 这些研究为解释Sl（d）表型提供了分子基础，描述了膜结合生长因子的跨膜和胞质结构域中的种系突变，并为膜结合形式的生长因子在哺乳动物发育中的重要性提供了体内证据。
Mice homozygous for the viable Sl allele steel-Dickie (Sl(d)) are sterile, severely anemic, and black-eyed white. The nature of the Sl(d) mutation was investigated at the molecular level and was found to be due to a 4.0-kilobase intragenic deletion in mast cell growth factor (MGF) genomic sequences, providing conclusive evidence that Sl encodes MGF. As a consequence of this deletion, Sl(d) is only capable of encoding a soluble truncated growth factor that lacks both transmembrane and cytoplasmic domains. Northern analysis indicates that Sl(d) mRNA is expressed at approximately wild-type levels in adult tissues, and yeast expression studies suggest that the Sl(d) protein is as biologically active as wild-type soluble MGF. These studies provide a molecular basis for explaining the Sl(d) phenotype, a description of a germ-line mutation in the transmembrane and cytoplasmic domains of a membrane-bound growth factor, and in vivo evidence for the importance of membrane-bound forms of growth factors in mammalian development.