title: Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis.
abstract: A mutation was targeted to the murine alpha3 integrin gene. Homozygous mutant mice survived to birth, but died during the neonatal period. The mutation caused abnormal kidney and lung development. Mutant kidneys displayed decreased branching of the medullary collecting ducts, although the number of nephrons was not altered. Proximal tubules exhibited two distinct subsets of abnormalities, with the epithelial cells either containing excess lysosomes or becoming microcystic. In addition, glomerular development was markedly affected. In mutant kidneys, the extent of branching of glomerular capillary loops was decreased, with capillary lumina being wider than normal. The glomerular basement membrane was disorganized and glomerular podocytes were unable to form mature foot processes. Branching of the bronchi in lungs of mutant mice was also decreased and the large bronchi extended to the periphery. These results indicate a role for integrin receptors in basement membrane organization and branching morphogenesis.
authors.affiliation: Division of Nephrology, Children's Hospital, Boston, MA 02115, USA. Kreidberg@a1.tch.harvard.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Kreidberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Donovan
authors.forename: S L
authors.initials: SL
authors.lastname: Goldstein
authors.forename: H
authors.initials: H
authors.lastname: Rennke
authors.forename: K
authors.initials: K
authors.lastname: Shepherd
authors.forename: R C
authors.initials: RC
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001485:Basement Membrane / Q000648:ultrastructure; D039422:Integrin alpha3; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D007668:Kidney / Q000196:embryology*; D007678:Kidney Glomerulus / Q000196:embryology; D008168:Lung / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis
chemical_list: D015703:Antigens, CD; D039422:Integrin alpha3; D019012:Integrin beta1; D016023:Integrins