Shull M M, Ormsby I, Kier A B, Pawlowski S, Diebold R J, Yin M, Allen R, Sidman C, Proetzel G, Calvin D
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524.
Nature. 1992 Oct 22;359(6397):693-9. doi: 10.1038/359693a0.
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
转化生长因子-β1(TGF-β1)是一种多功能生长因子,对许多发育和生理过程具有深远的调节作用。通过在小鼠胚胎干细胞中进行同源重组来破坏TGF-β1基因,能够产生携带破坏等位基因的小鼠。纯合突变TGF-β1等位基因的动物没有明显的发育异常,但出生后约20天,它们会死于消瘦综合征,伴有多灶性混合性炎症细胞反应和组织坏死,导致器官衰竭和死亡。TGF-β1缺陷小鼠可能是人类免疫和炎症性疾病的有价值模型,包括自身免疫性疾病、移植排斥反应和移植物抗宿主反应。