Mapping genetic determinants of kidney damage in rat models.
During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.
Department of Clinical Pharmacology and Toxicology, Charité Centrum für Therapieforschung, Charité - Universitätsmedizin Berlin, Berlin, Germany. angela-martina.schulz@charite.de
Angela
A
Schulz
Reinhold
R
Kreutz
D000818:Animals; D002874:Chromosome Mapping; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D011507:Proteinuria / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats; D011915:Rats, Inbred BUF; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR