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Distinct and common developmental expression patterns of the murine Pkd2 and Pkd1 genes
1Institut de Recherches Cliniques de Montreal, Molecular Genetics and Development, Faculte de Medecine de L'Universite de Montreal, Quebec, Canada.
Insights
Autosomal dominant polycystic kidney disease (ADPKD) involves a failure to exit renal development. Comparative Pkd1 and Pkd2 gene expression analysis reveals distinct patterns, particularly in kidney tubular epithelium.
Area of Science:
- Genetics
- Developmental Biology
- Nephrology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited renal disorder.
- The disease is linked to mutations in the PKD1 and PKD2 genes.
- ADPKD pathogenesis involves a failure to transition from renal developmental programs.
Purpose of the Study:
- To conduct a detailed comparative expression analysis of Pkd1 and Pkd2.
- To investigate gene expression from the morula stage to adulthood in mice.
- To identify differences in Pkd1 and Pkd2 expression patterns.
Main Methods:
- Comparative gene expression analysis.
- Study of murine models from embryonic to adult stages.
- Localization of Pkd1 and Pkd2 expression in developing tissues.
Main Results:
- Pkd2 expression, like Pkd1, is present from the morula stage and in mesenchymal/cartilaginous tissues.
- Unlike Pkd1, Pkd2 shows low/undetectable expression in neural crest-derived tissues.
- Pkd2 expression does not increase during mesenchymal condensation and is high in kidney tubular epithelium.
Conclusions:
- Pkd1 and Pkd2 exhibit distinct expression patterns during murine development.
- These differences may contribute to the specific mechanisms underlying ADPKD.
- Pkd2's localization in kidney tubular epithelium is a key finding for understanding ADPKD.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited renal diseases. At least two genes, PKD2 and PKD1 are implicated in the development of this disease. Our pathogenetic studies showed that the human and murine polycystic kidney disease (PKD) involves failure to switch out of a renal developmental program. We have thus undertaken a detailed comparative expression analysis of Pkd2 and Pkd1 from the morula stage to adulthood. Pkd2 expression was detected as early as the morula and blastocyst stages as observed for Pkd1. Strong Pkd2 expression, similar to Pkd1, was displayed in all mesenchymal and cartilaginous tissues during mouse development. However major differences in Pkd2 expression in comparison to Pkd1 were identified. First, in contrast to Pkd1, the neural crest cell-derived tissues displayed a low to undetectable Pkd2 expression at all ages. Second, no increase in Pkd2 expression was detected during mesenchymal condensation. Third, high Pkd2 expression in the kidneys was localized mainly to the tubular epithelium of the cortical region from murine development to adulthood.