Nephron deficit is not required for progressive proteinuria development in the Munich Wistar Frömter rat.
The Munich Wistar Frömter (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-8(SHR) by transfer of chromosome 8 from spontaneously hypertensive rats (SHR) into MWF. The early onset of albuminuria at 8 wk of age in MWF (>50-fold increase compared with SHR) was significantly suppressed in consomic animals, and the development of marked proteinuria at 32 wk significantly diminished. Total nephron number in consomic rats (23,771 +/- 1,352) and MWF (27,028 +/- 1,322) were similar and significantly lower (-36%) compared with SHR (36,979 +/- 1,352, P < 0.0001). The development of mild albuminuria in female MWF was also significantly diminished in MWF-8(SHR). 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-8(SHR) animals despite their inherited nephron deficit and higher systolic blood pressure.
Schulz
Angela
A
Department of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité-Universitätsmedizin Berlin, Berlin, Germany. angela.schulz@charite.de
Hänsch
Jonna
J
Kuhn
Kristina
K
Schlesener
Maria
M
Kossmehl
Peter
P
Nyengaard
Jens R
JR
Wendt
Norbert
N
Huber
Matthias
M
Kreutz
Reinhold
R
D000419:Albuminuria / Q000209:etiology* / Q000235:genetics; D000818:Animals; D020296:Animals, Congenic; D033481:Chromosomes, Mammalian / Q000235:genetics; D005260:Female; D006973:Hypertension / Q000150:complications; D008297:Male; D009399:Nephrons / Q000166:cytology*; D051381:Rats; D011918:Rats, Inbred SHR; D012727:Sex Characteristics