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

Evaluation of Rab38 as a new tubular candidate gene for albuminuria in MWF and Dahl SS rats

Evaluierung von Rab38: ein neues tubuläres Kandidatengen für Albuminurie bei MWF- und Dahl SS-Ratten

Meeting Abstract

  • A. Schulz - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • M. Wehland von Trebra - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • J. Weiss - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • J. Bolbrinker - Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, D)
  • R. Kreutz - 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. Doc05hochP157

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch157.shtml

Published: August 8, 2006

© 2006 Schulz et al.
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Outline

Text

Rab38 represents a small GTP binding protein that maps within the Rf-2 locus on rat chromosome (RNO) 1. It was identified as the first gene related to increased albumin excretion (UAE) in the fawn-hooded hypertensive (FHH) rat model. FHH animals carry a missense mutation in the translation initiation codon of Rab38 abolishing translation of Rab38 protein. In the kidney, Rab38 deficiency may contribute to increased UAE by impairment of reabsorption and processing of filtered protein in proximal tubular cells. We therefore tested the relevance of Rab38 as a candidate gene on RNO1 in the Munich Wistar Frömter (MWF) and Dahl-SS (SS) rat, in which UAE QTL have been mapped in the vicinity of Rab38. Analysis of the complete coding sequence including the start codon and flanking regions of Rab38 in MWF, SS and in Lewis and SHR reference strains revealed no differences. Thus, we can exclude the possibility that molecular variants in Rab38 cDNA are a cause of increased UAE in the SS strain and most importantly in the MWF strain in which a clear co-localization of an UAE QTL with Rab38 was identified. Quantitative mRNA analysis in kidney of adult male animals revealed a significant reduction of Rab38 expression in MWF and SS compared to Lewis and SHR (p<0.01, respectively; maximum reduction -64% in MWF compared to SHR). Thus, it appears of interest to further test the functional relevance of Rab38 and reduced Rab38 expression levels in MWF and SS in congenic strains derived from both strains.