Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis

Jordan A. Kreidberg, Michael J. Donovan, Stuart L. Goldstein, Helmut Rennke, Kenneth Shepherd, Rosemary C. Jones, Rudolf Jaenisch

Research output: Contribution to journalArticlepeer-review

624 Scopus citations

Abstract

A mutation was targeted to the murine α3 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.

Original languageEnglish
Pages (from-to)3537-3547
Number of pages11
JournalDevelopment (Cambridge)
Volume122
Issue number11
StatePublished - 1996
Externally publishedYes

Keywords

  • Alpha 3 beta 1 integrin
  • Basement membrane
  • Branching morphogenesis
  • Kidney
  • Lung
  • Mouse

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