Genetic predisposition for glomerulonephritis-induced glomerulosclerosis in rats is linked to chromosome 1.
Genetic factors influence renal disease progression, and several loci have been linked to the spontaneous development of proteinuria and glomerulosclerosis in animal models. However, the role of genetic susceptibility in glomerulonephritis-induced progressive glomerulosclerosis is unknown. In a rat model of mesangial proliferative glomerulonephritis, anti-Thy-1 glomerulonephritis (antiThy1GN), Lewis/Maastricht (Lew/Maa) rats exhibit progression to glomerulosclerosis, whereas in genetically related Lewis/Møllegard (Lew/Moll) rats, glomerular lesions are repaired within 3 wk. The genetic factors underlying this strain-related difference are not known. To identify novel quantitative trait loci (QTL) involved in progression or repair in Lewis rats, 145 female backcross rats [F1(Lew/Maa x Lew/Moll) x Lew/Maa] were studied. After induction of antiThy1GN proteinuria, we determined mesangial activation, the percentage of microaneurysms, and the glomerular damage score for each animal; a genome scan using 187 microsatellite markers was performed. QTL mapping revealed a significant QTL for glomerular damage score on chromosome 1 with a logarithm of odds (LOD) score of 3.9. Homozygosity for Lew/Maa DNA in this region was associated with a higher percentage of damaged glomeruli on day 21. Furthermore, suggestive linkage was found for the percentage of glomeruli with microaneurysms on day 3 on chromosome 1, 6, and 11; for mesangial activation on day 7 on chromosome 18, while proteinuria was suggestively linked to chromosome 5 (day 0), 4 (day 3), and 6 (day 7). This study identifies a QTL on rat chromosome 1 that is significantly linked to progressive glomerulosclerosis after acute glomerulonephritis.
Ijpelaar
Daphne H T
DH
Pathology, Leiden University Medical Center, Leiden, The Netherlands. d.ijpelaar@lumc.nl
Schulz
Angela
A
Aben
Joris
J
van der Wal
Annemieke
A
Bruijn
Jan A
JA
Kreutz
Reinhold
R
de Heer
Emile
E
D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000150:complications / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000473:pathology; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains