α3β1 integrin is highly expressed on a subset of renal epithelial cells and is a putative receptor for the extracellular matrix (ECM) components laminin, entactin, collagen and fibronectin. We are studying mice carrying a targeted mutation to the α3 integrin gene to determine if this ECM receptor is required during organogenesis. Homozygous mutants die during the first day of life and there is no α3β1 protein on mutant renal epithelial cells detected by immunofluorescent (IF) antibody staining. Heterozygous mice have a normal phenotypic appearance. There are several abnormalities in the mutant kidneys. Most strikingly, electron microscopic(EM) examination of mutant glomeruli demonstrates an inability of podocytes to form mature foot processes. Some mutant proximal tubules are dilated while others demonstrate an increased number of lysosomes and contain an increased amount of cytoplasmic Type IV collagen. IF staining has revealed disordered glomerular and tubular basement membranes (BM) in mutant kidneys. Specifically, entactin, laminin 1, and laminin β1 staining show a ragged and discontinuous BM. Examination of proximal tubules by EM reveals a poorly defined BM. Type IV collagen subtypes α1,2 appear normal in mutants by IF, but, subtypes α3,4,5 show an aberrant apical distribution in the cortical tubules of newborn mutants. Basolateral control markers are distributed normally in mutant tubules. Type IV collagen subtypes α3,4,5 are not expressed in wild-type newborn tubules.

The bronchi of mutant lungs are wider than normal and terminal bronchiolar branching is decreased in mutant lungs. IF staining for laminin β1 in mutant lung shows disordered BM as early as day 14 of gestation.

These results demonstrate that α3β1 integrin is required for proper morphological development during organogenesis. These findings also raise the possibility that deficiency of α3β1 integrin results in defects in epithelial differentiation and branching morphogenesis.