gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Early onset renal damage in the MWF rat can be eliminated by genetic replacement of chromosome 6 in a consomic strain

Die frühzeitige Manifestation der Nierenschädigung bei der MWF-Ratte kann durch genetischen Austausch von Chromosom 6 aufgehoben werden

Meeting Abstract

  • J. Weiss - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • M. Wehland - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • N. Wendt - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • R. Kreutz - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • A. Schulz - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP46

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch046.shtml

Veröffentlicht: 8. August 2006

© 2006 Weiss 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

In a recent crossbreeding study between Munich Wistar Frömter rats (MWF) and spontaneously hypertensive rats (SHR) we identified quantitative trait loci (QTL) for albuminuria in MWF. A major gene locus on chromosome 6 (RNO6) was linked to early onset albuminuria and renal interstitial fibrosis in male MWF animals. We generated a speed consomic strain to test the relevance of this QTL to the development of proteinuric renal disease. In accordance to the cosegregation analysis we used the SHR as a contrasting reference strain which shows similar hypertension compared to the MWF rats but normal urinary albumin excretion (UAE) levels. A consomic MWF-6SHR was generated by sequential marker-assisted backcrossing transferring chromosome 6 from SHR into MWF rats. The MWF background and an intact SHR chromosome 6 in the consomic strain were confirmed by genome analysis with 238 microsatellite markers.

At 8 weeks of age 24h urine of male animals was collected in metabolic cages (n=10-19, respectively). For determination of UAE a rat albumin specific ELISA-assay was utilized. UAE in parental MWF rats was significantly higher compared to SHR animals (18.78 +/- 8.19 vs. 0.33 +/- 0.23 mg/24h, p<0.001). The MWF-6SHR rats showed normal UAE levels (0.71 +/- 0.50 mg/24h) that were significantly lower compared to MWF rats (p<0.001) but not different from SHR or other strains with normal renal function.

Although albuminuria and renal interstitial fibrosis which lead to end-stage renal disease in the MWF rat are polygenetic traits our data show that RNO6 contains at least one gene that has a decisive influence on the early development of renal damage.