gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Genome scan analysis in the MWF rat identifies a major gene locus for early onset albuminuria linked to renal interstitial fibrosis

Identifizierung eines bedeutenden Genortes für die frühe Manifestation der Albuminurie und interstitielle Nierenfibrose

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker A. Schulz
  • D. Standke
  • L. Kovacevic
  • M. Mostler
  • P. Kossmehl
  • M. Stoll

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV29

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch029.shtml

Veröffentlicht: 11. November 2004

© 2004 Schulz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Renal interstitial fibrosis (RIF) has been implicated in the progression of chronic proteinuric nephropathies. The Munich Wistar Frömter (MWF) rat represents a genetic animal model that develops a significant elevation of urinary albumin excretion (UAE) and RIF compared to spontaneously hypertensive rats (SHR) with normal renal function. We analyzed the genetic basis of UAE in relation to RIF by using a genetic linkage and quantitative trait loci (QTL) mapping strategy. F1-hybrids generated from a cross between MWF and SHR rats demonstrated normal UAE rates similar to SHR. We therefore generated a (SHR x MWFFUB) x MWFFUB backcross population including 215 male animals. To investigate the age of onset effect, UAE was determined in young backcross animals at 8 weeks and in adult animals at 14 and 24 weeks of age, respectively. RIF was evaluated by Sirius red staining of kidney sections and quantified by computer-assisted image analysis at 24 weeks. Total genome scan analysis identified eight QTL linked to UAE and a major locus on chromosome 6 (RNO6). At this locus, homozygosity for the MWF allele demonstrated a 3fold increased UAE and displayed significant linkage already at 8 weeks (LOD=4.3) with increasing significance at 14 and 24 weeks of age (LOD 7.8 and 10.1, respectively). The QTL on RNO6 was also significantly linked to the amount of RIF (p<0.0009, Lod 2.4). Thus, the results on RNO6 indicated a genetic link between early onset albuminuria and the progression of RIF. Currently, we aim to identify the genetic basis for RNO6 to obtain new insights into the progression of proteinuric renal disease.