Suleiman, Hani and Heudobler, Daniel and Raschta, Anne-Sarah and Zhao, Yangu and Zhao, Qi and Hertting, Irmgard and Vitzthum, Helga and Moeller, Marcus J. and Holzman, Lawrence B. and Rachel, Reinhard and Johnson, Randy and Westphal, Heiner and Rascle, Anne and Witzgall, Ralph (2007) The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Developmental biology 304 (2), pp. 701-712.
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Patients with nail-patella syndrome, which among other symptoms also includes podocyte-associated renal failure, suffer from mutations in the LMX1B gene. The disease severity among patients is quite variable and has given rise to speculations on the presence of modifier genes. Promising candidates for modifier proteins are the proteins interacting with LMX1B, such as LDB1 and E47. Since human kidney samples from patients are difficult to obtain, conventional Lmx1b knock-out mice have been extremely valuable to study the role of Lmx1b in podocyte differentiation. In contrast to findings in these mice, however, in which a downregulation of the Col4a3, Col4a4 and Nphs2 genes has been described, no such changes have been detected in kidney biopsies from patients. We now report on our results on the characterization of constitutive podocyte-specific Lmx1b, Ldb1 and E2a knock-out mice. Constitutive podocyte-specific Lmx1b knock-out mice survive for approximately 2 weeks after birth and do not present with a downregulation of the Col4a3, Col4a4 and Nphs2 genes, therefore they mimic the human disease more closely. The podocyte-specific Ldb1 knock-out mice survive longer, but then also succumb to renal failure, whereas the E2a knock-out mice show no renal symptoms for at least 6 months after birth. We conclude that LDB1, but not E2A is a promising candidate as a modifier gene in patients with nail-patella syndrome.
|Institutions:||Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie > Prof. Dr. Michael Thomm|
|Subjects:||500 Science > 570 Life sciences|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||22 Mar 2010 08:11|
|Last Modified:||22 Mar 2010 08:11|