Constitutive metanephric mesenchyme-specific expression of interferon-gamma causes renal dysplasia by regulating Sall1 expression

PloS One
Kangsun YunAlan O Perantoni

Abstract

Transplacental viral and parasitic infections have been shown to initiate an innate response in the mammalian embryo by increasing the expression of pro-inflammatory cytokines such as interferon-gamma (Ifng). However, the developmental consequences of an activated innate immunity and, in particular, the effects of induction of Ifng expression independent of infection have been largely overlooked. Here, we demonstrate in vivo that the conditional overexpression of Ifng in metanephric mesenchymal (MM) progenitors results in renal agenesis or hypoplasia. Cell death was observed in and around the MM region of E10.5-11.5 mutants where Ifng was constitutively expressed during early kidney development and resulted in a retardation of branching morphogenesis. Furthermore, isolated mutant or normal Ifng-treated metanephroi replicated this phenotype in culture, demonstrating the inherent nature of the aberrant morphogenesis. The expression of renal progenitor marker Sall1 was significantly decreased in the MM of mutant kidneys, suggesting that a reduction in Sall1 may be the cause of cell death in the MM during early kidney development and that, in turn, retards UB branching in the mutants. Therefore, the aberrant induction of Ifng expre...Continue Reading

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Methods Mentioned

BETA
genotyping
ELISA
PCR
transgenic
ubiquitination

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