通过对小鼠进行靶向基因敲除所揭示的哺乳动物Smad基因的功能。

Functions of mammalian Smad genes as revealed by targeted gene disruption in mice.

作者信息

Weinstein M, Yang X, Deng C

机构信息

Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10/9N105, 10 Center Drive, Bethesda, MD 20892, USA.

出版信息

Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):49-58. doi: 10.1016/s1359-6101(99)00028-3.

DOI:10.1016/s1359-6101(99)00028-3

PMID:10708952

Abstract

The Smad genes are the intracellular mediators of TGF-beta signals. Targeted mutagenesis in mice has yielded valuable new insights into the functions of this important gene family. These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton. In addition, these experiments have shown us the importance of gene dosage in this family, as several of its members yielded haploinsufficiency phenotypes. These include gastrulation and craniofacial defects for Smad2, accelerated wound healing for Smad3, and the incidence of gastric cancer for Smad4. Combinatorial genetics has also revealed functions of Smads in left/right isomerism and liver development.

摘要

Smad基因是转化生长因子-β（TGF-β）信号的细胞内介质。对小鼠进行的靶向诱变，为深入了解这个重要基因家族的功能带来了宝贵的新见解。这些实验表明，原肠形成需要Smad2和Smad4，血管生成需要Smad5，黏膜免疫反应的建立和骨骼的正常发育需要Smad3。此外，这些实验还向我们展示了该基因家族中基因剂量的重要性，因为其几个成员产生了单倍剂量不足的表型。这些表型包括Smad2导致的原肠形成和颅面缺陷、Smad3导致的伤口愈合加速以及Smad4导致的胃癌发病率。组合遗传学也揭示了Smad在左右异构和肝脏发育中的功能。