Charakterisierung induzierbarer, podozytenspezifischer Lmx1b Knock-out Mäuse

Magdalena Emma Schaffer
2014
The nail-patella syndrome has an incidence of about 1:50.000 and is characterized by deformities of the nails, knees, elbows as well as by an affection of the kidney and the eyes (Sweeney E et al., 2003). Yet decisive for the prognosis of patients is the degree of affection of the kidney. LMX1B, localized on chromosome 9q34, was identified as the gene being responsible for the disease (McIntosh I et al., 1997). Since then, several animal models have been developed to improve the understanding
more » ... the understanding of the pathogenesis of NPS. The aim of this study was to further characterize these diverse mouse models. First, the conventional Lmx1b knock-out mice should be mentioned, as homozygous animals resemble the human NPS (Chen H et al., 1998) while animals with an heterozygous genotype do not show an noticeable phenotype (Rohr C et al., 2002). In this study, we could show a higher susceptibility for developing proteinuria in Lmx1b+/- mice than in Lmx1b+/+ mice after injection of anti-GBM serum. So perhaps there is an phenotype in heterozygous animals in form of a higher susceptibility to nephrotoxic influences. Other experiments with different nephrotoxic effects were however disappointing and could reveal no difference between the two genotypes. Another aim of this study was to further characterize mice with an podocyte-specific inactivation of Lmx1b. In contrast to conventional Lmx1b knock-out mice, they showed no noticeable reaction to the injection of anti-GBM serum, so you might think that a systemic influence of Lmx1b is responsible for the observed effect in conventional Lmx1b knock-out mice. Another essay to improve understanding of the function of Lmx1b was the analysis of messenger- RNA isolated from glomerula of mice with an inducible podocyte-specific inactivation of Lmx1b. There we found hints for a role of Lmx1b in the regulation of genes with impact on the immune system, on cell adhesion, motility and communication. Last, we examined survival of different genotypes of the line Rb-lox3 (926) x Lmx1b2loxP x P2.5-Cre [...]
doi:10.5283/epub.24427 fatcat:m5g6svxoerhavdbku22f7xtp5u