Submitted on June 10, 2008
Revised on July 8, 2008
Accepted on July 16, 2008
A nephron deficit is not required for progressive proteinuria development in the Munich Wistar Fromter rat
Angela Schulz1*, Jonna Hansch1, Kristina Kuhn1, Maria Schlesener1, Peter Kossmehl1, Jens R. Nyengaard2, Norbert Wendt1, Matthias Huber1, and Reinhold Kreutz3
1 Charite - Universitatsmedizin Berlin, CBF/CCM
2 University of Aarhus
3 Charite University Medicine Berlin
* To whom correspondence should be addressed. E-mail: angela.schulz{at}charite.de.
The Munich Wistar Fromter (MWF) rat represents a genetic model with an inherited nephron deficit and exhibits mild hypertension and progressive albuminuria, which is more pronounced in males than females. Previously, we demonstrated in a consomic strain that replacement of a quantitative trait locus on chromosome 6 normalized the nephron deficit and suppressed albuminuria development suggesting a link between the two findings. Here we tested the role of a second major locus linked to albuminuria in MWF on chromosome 8 and generated the consomic strain MWF-8SHR by transfer of chromosome 8 from spontaneously hypertensive rats (SHR) into MWF. The early onset of albuminuria at 8 weeks of age in MWF (>50fold increase compared to SHR) was significantly suppressed in consomic animals and the development of marked proteinuria at 32 weeks significantly diminished. Total nephron number in consomic rats (23771±1352) and MWF (27028±1322) were similar andsignificantly lower (-36%) compared to SHR (36979±1352, p<0.0001). The development of mild albuminuria in female MWF was also significantly diminished in MWF-8SHR. Thus, the development of overt and mild albuminuria in male and female MWF rats is not a mandatory consequence of the inherited nephron deficit. The locus on chromosome 8 appears of interest, because its exchange between MWF and SHR protects against the development of albuminuria in MWF-8SHR animals despite their inherited nephron deficit and higher systolic blood pressure.
