Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia.
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.
Gründer
Albert
A
Institut fur Biologie III, Albert-Ludwigs-Universitat, Freiburg, Germany.
Ebel
Thorsten T
TT
Mallo
Moisés
M
Schwarzkopf
Georg
G
Shimizu
Takehiko
T
Sippel
Albrecht E
AE
Schrewe
Heinrich
H
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology; D008171:Lung Diseases / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D051839:NFI Transcription Factors; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000096:biosynthesis
D018076:DNA, Complementary; D053823:Hedgehog Proteins; D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; D011506:Proteins; D015534:Trans-Activators