Letterio J J, Geiser A G, Kulkarni A B, Roche N S, Sporn M B, Roberts A B
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Science. 1994 Jun 24;264(5167):1936-8. doi: 10.1126/science.8009224.
Maternal sources of transforming growth factor-beta 1 (TGF-beta 1) are shown here to contribute to the normal appearance and perinatal survival of TGF-beta 1 null newborn mice. Labeled TGF-beta 1 crossed the placenta and was recovered intact from various tissues after oral administration to mouse pups. TGF beta-1 protein was also detected in cells recovered from breast milk. In immunohistochemical analyses, TGF-beta 1 null embryos and null newborn pups born to TGF-beta 1 heterozygotes stained positive for TGF-beta 1, whereas those born to a null female were negative and had severe cardiac abnormalities. These results suggest an important role for maternal sources of TGF-beta 1 during development and, more generally, provide evidence for maternal rescue of targeted gene disruption in the fetus.
本文显示,转化生长因子-β1(TGF-β1)的母体来源有助于TGF-β1基因敲除新生小鼠的正常外观和围产期存活。标记的TGF-β1穿过胎盘,并在给幼鼠口服后从各种组织中完整回收。在从母乳中回收的细胞中也检测到了TGF-β1蛋白。在免疫组织化学分析中,TGF-β1杂合子所生的TGF-β1基因敲除胚胎和新生幼崽对TGF-β1染色呈阳性,而由基因敲除雌性所生的胚胎和幼崽则为阴性,且有严重的心脏异常。这些结果表明母体来源的TGF-β1在发育过程中具有重要作用,更普遍地说,为胎儿中靶向基因破坏的母体拯救提供了证据。