Gründer Albert, Ebel Thorsten T, Mallo Moisés, Schwarzkopf Georg, Shimizu Takehiko, Sippel Albrecht E, Schrewe Heinrich
Institut fur Biologie III, Albert-Ludwigs-Universitat, Freiburg, Germany.
Mech Dev. 2002 Mar;112(1-2):69-77. doi: 10.1016/s0925-4773(01)00640-2.
Binding sites for transcription factor nuclear factor one (NFI) proteins, encoded by four genes in the mouse, have been characterized from many tissue-specific genes. NFI genes are expressed in unique but overlapping patterns in embryonic and in adult tissues. Nfib is highly expressed in the embryonic lung. Here we show that Nfib null mutants die early postnatally and display severe lung hypoplasia. Heterozygotes do survive, but exhibit delayed pulmonary differentiation. Expression of transforming growth factor beta 1 (TGF-beta1) and sonic hedgehog (Shh) is not down-regulated in mutant lung epithelium at late stages of morphogenesis, which may result in incomplete lung maturation. Our study demonstrates that Nfib is essential for normal lung development, and suggests that it could be involved in the pathogenesis of respiratory distress syndromes in humans.
转录因子核因子一（NFI）蛋白的结合位点已从许多组织特异性基因中得到表征，该蛋白由小鼠中的四个基因编码。NFI基因在胚胎组织和成年组织中以独特但重叠的模式表达。Nfib在胚胎肺中高度表达。在这里，我们表明Nfib基因敲除突变体在出生后早期死亡，并表现出严重的肺发育不全。杂合子能够存活，但表现出肺分化延迟。在形态发生后期，突变肺上皮中转化生长因子β1（TGF-β1）和音猬因子（Shh）的表达未下调，这可能导致肺成熟不完全。我们的研究表明，Nfib对正常肺发育至关重要，并提示它可能参与人类呼吸窘迫综合征的发病机制。
