Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice
Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice
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DOI：
10.1128/mcb.24.10.4448-4464.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Nielsen, FC
中科院分区：
文献类型：
--
作者：
Hansen, TVO;Hammer, NA;Nielsen, FC
胰岛素样生长因子 II mRNA 结合蛋白 1 (IMP1) 属于与 mRNA 定位、周转和翻译控制有关的 RNA 结合蛋白家族。小鼠 IMP1 在早期发育过程中表达，并且在胚胎第 12.5 天 (E12.5) 左右表达增加。为了表征 IMP1 的生理作用，我们培育了 IMP1 缺陷型小鼠，该小鼠在 Imp1 基因中插入了基因陷阱。 Imp1(-/-) 小鼠比野生型和杂合性同窝小鼠平均小 40%。生长迟缓从 E17.5 开始就很明显，并且在成年后仍永久存在。此外，Imp1(-/-)小鼠表现出较高的围产期死亡率，出生后3天仅50%存活。与大多数其他器官相反，肠上皮细胞在出生后继续表达IMP1，Imp1(-/-)小鼠表现出肠道发育受损，绒毛小而畸形，结肠隐窝扭曲。 E12.5 的靶 mRNA 分析和全局表达谱分析表明 Igf2 翻译下调，而出生后肠道显示编码细胞外基质成分的转录物表达减少，例如半乳糖凝集素-1、lumican、tenascin-C、前胶原转录物和 Hsp47 前胶原伴侣。综上所述，结果表明 IMP1 对于正常生长和发育至关重要。此外，IMP1 可能通过调节细胞外基质形成来促进肠道形态发生。
Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). To characterize the physiological role of IMP1, we generated IMP1-deficient mice carrying a gene trap insertion in the Imp1 gene. Imp1(-/-) mice were on average 40% smaller than wild-type and heterozygous sex-matched littermates. Growth retardation was apparent from E17.5 and remained permanent into adult life. Moreover, Imp1(-/-) mice exhibited high perinatal mortality, and only 50% were alive 3 days after birth. In contrast to most other organs, intestinal epithelial cells continue to express IMP1 postnatally, and Imp1(-/-) mice exhibited impaired development of the intestine, with small and misshapen villi and twisted colon crypts. Analysis of target mRNAs and global expression profiling at E12.5 indicated that Igf2 translation was downregulated, whereas the postnatal intestine showed reduced expression of transcripts encoding extracellular matrix components, such as galectin-1, lumican, tenascin-C, procollagen transcripts, and the Hsp47 procollagen chaperone. Taken together, the results demonstrate that IMP1 is essential for normal growth and development. Moreover, IMP1 may facilitate intestinal morphogenesis via regulation of extracellular matrix formation.