Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome

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Item Type:	Article
Title:	Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome
Creators Name:	Ratelade, J., Lavin, T.A., Muda, A.O., Morisset, L., Mollet, G., Boyer, O., Chen, D.S., Henger, A., Kretzler, M., Huebner, N., Thery, C., Gubler, M.C., Montagutelli, X., Antignac, C. and Esquivel, E.L.
Abstract:	Mutations in the NPHS2 gene, which encodes podocin, are responsible for some cases of sporadic and familial autosomal recessive steroid-resistant nephrotic syndrome. Inter- and intrafamilial variability in the progression of renal disease among patients bearing NPHS2 mutations suggests a potential role for modifier genes. Using a mouse model in which the podocin gene is constitutively inactivated, we sought to identify genetic determinants of the development and progression of renal disease as a result of the nephrotic syndrome. We report that the evolution of renal disease as a result of nephrotic syndrome in Nphs2-null mice depends on genetic background. Furthermore, the maternal environment significantly interacts with genetic determinants to modify survival and progression of renal disease. Quantitative trait locus mapping suggested that these genetic determinants may be encoded for by genes on the distal end of chromosome 3, which are linked to proteinuria, and on the distal end of chromosome 7, which are linked to a composite trait of urea, creatinine, and potassium. These loci demonstrate epistatic interactions with other chromosomal regions, highlighting the complex genetics of renal disease progression. In summary, constitutive inactivation of podocin models the complex interactions between maternal and genetically determined factors on the progression of renal disease as a result of nephrotic syndrome in mice.
Keywords:	Disease Progression, Environment, Genomics, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Nephrotic Syndrome, Phenotype, Animals, Mice
Source:	Journal of the American Society of Nephrology
ISSN:	1046-6673
Publisher:	American Society of Nephrology
Volume:	19
Number:	8
Page Range:	1491-1499
Date:	August 2008
Official Publication:	https://doi.org/10.1681/ASN.2007111268
PubMed:	View item in PubMed

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