Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

[junctional epidermolysis bullosa]

Mice with targeted disruption of the lama 3 gene , which encodes the alpha 3 chain of laminin-5 (alpha 3 beta 3 gamma 2 , 332 ), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans . These animals also develop abnormalities in glomerulogenesis . In both wild-type and mutant animals (lama 3 (-/-)), podocytes secrete glomerular basement membrane and develop foot processes . Endothelial cells migrate into this scaffolding and secrete a layer of basement membrane that fuses with the one formed by the podocyte . In lama 3 (-/-) animals , glomerular maturation arrests at this stage . Endothelial cells do not attenuate , develop fenestrae , or form typical lumens , and mesangial cells (MCs ) were not identified . LN alpha 3 subunit (LAMA 3 ) protein was identified in the basement membrane adjacent to glomerular endothelial cells (GEnCs ) in normal rats and mice . In developing rat glomeruli , the LAMA 3 subunit was first detectable in the early capillary loop stage , which corresponds to the stage at which maturation arrest was observed in the mutant mice . Lama 3 mRNA and protein were identified in isolated rat and mouse glomeruli and cultured rat GEnCs , but not MC . These data document expression of LAMA 3 in glomeruli and support a critical role for it in GEnC differentiation . Furthermore , LAMA 3 chain expression and /or another product of endothelial cells are required for MC migration into the developing glomerulus .

Diseases
Validation

Diseases presenting "skin disease" symptom

child syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

harlequin ichthyosis

junctional epidermolysis bullosa

kindler syndrome

lamellar ichthyosis

omenn syndrome

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