How are podocytes affected in nail-patella syndrome?
Nail-patella syndrome is an autosomal-dominant hereditary disease named for dysplastic fingernails and toenails and hypoplastic or absent kneecaps evident in patients with the syndrome. Prognosis is determined by the nephropathy that develops in many such patients. Besides podocyte foot-process effacement, pathognomonic changes in the kidney comprise electron-lucent areas and fibrillar inclusions in the glomerular basement membrane. These characteristic symptoms are caused by mutations in the gene encoding the transcription factor LMX1B, a member of the LIM-homeodomain gene family. Comparable with the human syndrome, homozygous Lmx1b knockout mice lack patellae and suffer from severe podocyte damage. In contrast, however, podocin and the alpha3 and alpha4 chains of collagen IV are absent in the glomeruli of Lmx1b knockout mice. Further studies with podocyte-specific Lmx1b knockout mice have confirmed the importance of LMX1B in podocytes, as these mice apparently develop foot processes initially but lose them later on. We therefore conclude that LMX1B is essential for the development of metanephric precursor cells into podocytes and possibly also for maintaining the differentiation status of podocytes. LMX1B can serve as a model system to elucidate a genetic program in podocytes.
Witzgall
Ralph
R
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009261:Nail-Patella Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors