Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects.
To uncover roles for the Hoxa-5 gene during embryogenesis, we have focused on identifying structural and functional defects in organ systems underlying the perinatal lethality in Hoxa-5 homozygous mutants. Analysis of the mutant phenotype shows that Hoxa-5 is essential for normal organogenesis and function of the respiratory tract. In homozygous newborn mutants, improper tracheal and lung morphogenesis can lead to tracheal occlusion, and to respiratory distress associated with a marked decrease in the production of surfactant proteins. Collectively, these defects likely underlie the pronounced mortality of homozygous mutant pups. Furthermore, the loss of Hoxa-5 function results in altered TTF-1, HNF-3 beta, and N-myc gene expression in the pulmonary epithelium. Since expression of Hoxa-5 is confined to the mesenchymal component of the developing trachea and lung, the effects observed in epithelial cells may result from a disruption of normal epithelial-mesenchymal interactions.
Aubin
J
J
Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, Canada.
Lemieux
M
M
Tremblay
M
M
Bérard
J
J
Jeannotte
L
L
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D005804:Genes, Lethal; D016259:Genes, myc; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins / Q000502:physiology*; D017403:In Situ Hybridization; D007830:Larynx / Q000002:abnormalities / Q000196:embryology; D008168:Lung / Q000002:abnormalities / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015619:Respiratory System Abnormalities / Q000196:embryology / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014132:Trachea / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; C496500:Foxa1 protein, mouse; C496503:Foxa2 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta