携带工程化突变型α1（I）前胶原基因的转基因小鼠中的围产期致死性成骨不全症

Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene.

作者信息

Stacey A, Bateman J, Choi T, Mascara T, Cole W, Jaenisch R

机构信息

Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142.

出版信息

Nature. 1988 Mar 10;332(6160):131-6. doi: 10.1038/332131a0.

DOI:10.1038/332131a0

PMID:2450280

Abstract

Substitutions of single glycine residues of alpha 1(I) collagen have previously been associated with the inherited disease osteogenesis imperfecta type II. Transgenic mice bearing a mutant alpha 1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.

摘要

先前已发现，α1（I）胶原蛋白单个甘氨酸残基的替换与遗传性II型成骨不全症有关。携带经基因工程改造具有特定甘氨酸替换的突变α1（I）胶原蛋白基因的转基因小鼠表现出人类疾病特有的显性致死表型，并表明低至10%的突变基因表达就能破坏正常的胶原蛋白功能。