Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development
Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development
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DOI：
10.1006/dbio.1997.8666
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发表时间：
1997-09-01
影响因子：
2.7
通讯作者：
Efstratiadis, A
中科院分区：
文献类型：
--
作者：
Louvi, A;Accili, D;Efstratiadis, A
对编码胰岛素样生长因子(IGF-I和IGF-II)及其同源1型IGF受体(IGF1R)的基因进行定向突变所产生的矮化表型的遗传分析表明，该信号系统是小鼠胚胎生长的主要决定因素。在两个IGE配体中，IGF-I只与IGF1R相互作用，而IGF-II识别一个额外的受体(XR)，因为缺乏IGR1R和IGF-II的胚胎(占正常出生体重的30%)比任何一类单一的IGF1R或IGF2缺失突变(分别是正常的45%和60%)表现出更严重的生长迟缓。为了确定XR是否是胰岛素受体(IR)，我们检查了胚胎中Igf1r和Insr的缺失型。虽然仅缺乏IR的胚胎的生长受到非常轻微的影响，仅在妊娠末期，伴随着IGF1R的缺乏会导致严重的生长缺陷表型(出生时正常大小的30%)，在胚胎13.5天首次发现，还表现为一过性水肿、卷尾、全身器官发育不全，包括肌肉、骨化发育延迟和表皮变薄。IGF1R/InsR双零合子与缺少IGF1R和IGF-II的双突变体以及其他已消除所有IGF配体/受体相互作用的双突变体和三重突变体没有明显的表型区别。因此，这些结果提供了遗传证据，证明IGF-II在小鼠胚胎发育过程中的促生长作用部分是通过胰岛素受体的信号传递来实现的。(C)1997年学术出版社。
Genetic analyses of dwarfing phenotypes resulting from targeted mutagenesis of the genes encoding the insulin-like growth factors (IGF-I and IGF-II) and their cognate type 1 IGF receptor (IGF1R) have demonstrated that this signaling system is a major determinant of mouse embryonic growth. Of the two IGE ligands, IGF-I interacts exclusively with IGF1R, whereas IGF-II recognizes an additional receptor (XR), because the growth retardation of embryos lacking both IGR1R and IGF-II (30% of normal birthweight) is more severe than that manifested in either class of single Igf1r or Igf2 null mutants (45 and 60% of normal, respectively). To determine whether XR is the insulin receptor (IR), we examined embryos nullizygons for both Igf1r and Insr. While the growth of embryos lacking solely IR is affected very mildly and only at the end of gestation, concomitant absence of IGF1R results in a severe growth-deficiency phenotype (30% of normal size at birth) that is first detected at Embryonic Day 13.5 and is also characterized by transient edema, curly tail, generalized organ hypoplasia, including the muscles, developmental delays in ossification, and thin epidermis. The Igf1r/Insr double nullizygotes are phenotypically indistinguishable from double mutants lacking IGF1R and IGF-II and from other double and triple mutants in which all of the IGF ligand/receptor interactions have been eliminated. Therefore, these results provide genetic evidence that the growth-promoting function of IGF-II during mouse embryogenesis is mediated in part by signaling through the insulin receptor. (C) 1997 Academic Press.