title: Induction of albuminuria and kidney damage in SHR by transfer of chromosome 8 from Munich Wistar Frömter rats.
abstract: Inbred Munich Wistar Frömter [MWF/FubRkb (RGD:724569), MWF] rats develop progressive albuminuria with age that is under polygenetic influence. We previously identified a major albuminuria quantitative trait locus (QTL) on rat chromosome (RNO)8 in MWF. To test the independent role of QTL(s) for albuminuria development on RNO8, we generated a consomic SHR-Chr 8(MWF)/Rkb (SHR-8(MWF)) strain by transferring RNO8 from MWF into the albuminuria-resistant background of the spontaneously hypertensive rat [SHR/FubRkb (RGD:631696; SHR)]. Young male MWF, SHR, and SHR-8(MWF) were sham-operated or unilaterally nephrectomized (Nx) at 6 wk and followed up to 24 wk of age, respectively. Systolic blood pressure was significantly lower in SHR-8(MWF) Sham compared with SHR Sham (-19.4 mmHg, P = 0.03) at 24 wk. In contrast, transfer of MWF-RNO8 into SHR induced a significant elevation of urinary albumin excretion (UAE) between weeks 12 and 24 in SHR-8(MWF) compared with SHR Sham animals (P < 0.0001, respectively). Nx resulted in a significant increase in UAE in both strains during follow-up (P < 0.0001, respectively), with significant higher values in SHR-8(MWF) compared with SHR (P < 0.005, respectively). Renal structural changes as determined by glomerulosclerosis (GSI) and tubulointerstitial damage index (TDI) were significantly higher in consomic animals either at Sham (TDI) or Nx (GSI) conditions (P < 0.05, respectively). These data confirm the independent role of MWF QTL(s) on RNO8 for both albuminuria and structural kidney damage. Moreover, this study shows for the first time the induction of albuminuria by transferring one or more albuminuria QTL into a resistant recipient background in a consomic rat strain.
authors: Department of Clinical Pharmacology and Toxicology, Charité Centrum für Therapieforschung, Charité - Universitätsmedizin Berlin, Berlin, Germany. angela-martina.schulz@charite.de
authors: Angela
authors: A
authors: Schulz
authors: Sabrina
authors: S
authors: Schütten-Faber
authors: Nicole
authors: N
authors: van Es
authors: Johannes
authors: J
authors: Unland
authors: Leonard
authors: L
authors: Schulte
authors: Peter
authors: P
authors: Kossmehl
authors: Emile
authors: E
authors: de Heer
authors: Reinhold
authors: R
authors: Kreutz
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000818:Animals; D020296:Animals, Congenic; D033481:Chromosomes, Mammalian / Q000235:genetics*; D018450:Disease Progression; D018014:Gene Transfer Techniques; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000473:pathology* / Q000652:urine; D007668:Kidney / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D017208:Rats, Wistar