Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21–q26

Jada Pasquale Yengkopiong

Dr John Garang Memorial University of Science and Technology, Faculty of Science and Technology, Bor, Republic of South Sudan

Background: Polycystic kidney disease (PKD) is a life-threatening disorder that affects the kidneys of millions of people across the world. The disease is normally inherited, but it can also be acquired, and leads to development of many cysts in the renal nephrons. In this study, the aim was to characterize PKD in the Lewis polycystic kidney (LPK) rat, the newest model for human PKD.
Methods: Mating experiments were performed between male LPK rats with PKD and female Brown Norway and Wistar Kyoto rats without PKD to raise second filial (F2) and backcross 1 (BC1) progeny, respectively. Rats that developed PKD were identified. Histological examination of the kidneys and liver was performed. Liver tissue samples were collected from each rat and used to extract DNA. The extracted DNA was amplified, and mapping and linkage analyses were performed to identify the quantitative trait locus that controlled the disease phenotypes.
Results: It was established that the disease was controlled by a recessive mutation in a single gene (F2: PKD = 42, non-PKD = 110, χ² = 0.53; BC1: PKD = 67, non-PKD = 72, χ² = 0.18, P > 0.05) and that the disease was inherited as autosomal recessive polycystic kidney disease (ARPKD). The rats with PKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia. However, there were no extrarenal cysts and no pup deaths. Mapping studies and linkage analyses associated the disease phenotypes in both the F2 and BC1 rats to chromosome 10q21–q26, giving a maximum LOD score of 7.9 (P = 0.00001) between peak markers D10Rat180 and D10Rat26.
Conclusion: The quantitative trait locus on chromosome 10q21–q26 does not contain the Pkhd-1 gene, and it is different from quantitative trait loci that control ARPKD in other murine models. The candidate genes located in the quantitative trait locus are important in signal transduction, cell growth, cell proliferation, and cell differentiation. Although expression of PKD in the LPK rat shares common phenotypic traits with ARPKD caused by mutation in Pkhd-1, the gene responsible for ARPKD in the LPK rat is different and unknown, or a mechanism yet to be identified is responsible for development of the disease.

Keywords: polycystic kidney disease, quantitative trait locus, signal transduction, cell proliferation