Dwarfism and Impaired Gut Development in Insulin-Like Growth Factor II mRNA-Binding Protein 1-Deficient Mice
AUTOR(ES)
Hansen, Thomas V. O.
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=400488Documentos Relacionados
- A Family of Insulin-Like Growth Factor II mRNA-Binding Proteins Represses Translation in Late Development
- Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.
- Impaired Hepatocyte DNA Synthetic Response Posthepatectomy in Insulin-Like Growth Factor Binding Protein 1-Deficient Mice with Defects in C/EBPβ and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Regulation
- Short hairpin RNA targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats
- Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function