Cover Image

Characterization of a major modifier locus for polycystic kidney disease (Modpkdr1) in the Han: SPRD(cy/+) rat in a region conserved with a mouse modifier locus for Alport syndrome

The genetic analysis of rodent disease models provides a powerful tool to investigate how modifier loci cause variation in the phenotypic expression of a disease. In order to test the existence of modifier loci influencing polycystic kidney disease (PKD) phenotypes, we derived a backcross between PK...

Full description

Saved in:
Bibliographic Details
Main Authors: Bihoreau, Marie-Thérèse (Author) , Megel, Natalia (Author) , Brown, Joanna H. (Author) , Kränzlin, Bettina (Author) , Crombez, Laurence (Author) , Tychinskaya, Yulia (Author) , Broxholme, John (Author) , Kratz, Susanne (Author) , Bergmann, Volker (Author) , Hoffmann, Sigrid (Author) , Gauguier, Dominique (Author) , Gretz, Norbert (Author)
Format: Article (Journal)
Language:English
Published: 01 September 2002
In: Human molecular genetics
Year: 2002, Volume: 11, Issue: 18, Pages: 2165-2173
ISSN:1460-2083
DOI:10.1093/hmg/11.18.2165
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/hmg/11.18.2165
Get full text
Author Notes:Marie-Thérèse Bihoreau, Natalia Megel, Joanna H. Brown, Bettina Kränzlin, Laurence Crombez, Yulia Tychinskaya, John Broxholme, Susanne Kratz, Volker Bergmann, Sigrid Hoffman, Dominique Gauguier and Norbert Gretz
Description
Summary:The genetic analysis of rodent disease models provides a powerful tool to investigate how modifier loci cause variation in the phenotypic expression of a disease. In order to test the existence of modifier loci influencing polycystic kidney disease (PKD) phenotypes, we derived a backcross between PKD susceptible Han:SPRD(cy/+) and control Brown Norway (BN) rats, and performed a whole-genome scan in 182 PKD affected hybrids showing different grades of disease severity. The genetic dissection of PKD in the cross allowed us to detect a modifier locus, Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma urea concentration. Results from database searches and computational analyses demonstrated that the Modpkdr1 locus shows strong evidence of synteny conservation with human and mouse chromosomal regions controlling kidney diseases, including disease progression of Alport syndrome. Comparative genome mapping also provided an inventory of potential candidate genes for modifier(s) of PKD. Analyses of the coding regions for four strong candidates (Ctsh, Bcl2a1, Trpc1 and Slc21a2) in (cy/+), BN and Lewis rat strains did not reveal sequence variants that could be associated with PKD. The characterization of Modpkdr1 may provide new insights into modulating mechanisms involved in the pathogenesis of PKD that could delay disease progression in humans. It may also have strong implications in the identification of pathophysiological factors common to different renal disorders.
Item Description:Gesehen am 24.06.2022
Physical Description:Online Resource
ISSN:1460-2083
DOI:10.1093/hmg/11.18.2165

Similar Items