Aarhus University Seal / Aarhus Universitets segl

Jens Randel Nyengaard

Development of overt proteinuria in the Munich Wistar Frömter rat is suppressed by replacement of chromosome 6 in a consomic rat strain.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Angela Schulz, Denmark
  • Judith Weiss, Denmark
  • Maria Schlesener, Denmark
  • Jonna Hänsch, Denmark
  • Markus Wehland, Denmark
  • Norbert Wendt, Denmark
  • Peter Kossmehl, Denmark
  • Anika Sietmann, Denmark
  • Daniela Grimm, Denmark
  • Monika Stoll, Denmark
  • Jens Randel Nyengaard
  • Reinhold Kreutz, Denmark
  • Stereological Research Laboratory
  • Institute of Clinical Medicine
  • The Department of Pathology - ÅKH
In a cross between the Munich Wistar Frömter (MWF) rat and spontaneously hypertensive rats (SHR), a major quantitative trait locus (QTL) was identified on rat chromosome 6 (RNO6) that demonstrated the strongest linkage to albuminuria among several QTL identified. The QTL represented the only locus that is linked to both early-onset albuminuria and increased renal interstitial fibrosis in adult animals. A consomic MWF-6(SHR) strain in which chromosome 6 from SHR was introgressed into the MWF background therefore was generated to test the relevance of this QTL. Phenotype analysis at 8 wk of age revealed that early onset of albuminuria in MWF with a 55-fold elevation of urinary albumin excretion compared with SHR (P < 0.0001) was completely abolished in MWF-6(SHR). Time-course analysis until week 24 demonstrated only a moderate increase of urinary albumin excretion in MWF-6(SHR), whereas MWF reached levels in the nephrotic range (16.6 +/- 3.5 versus 162.6 +/- 16.0 mg/24 h; P < 0.0001). At this age, analysis of glomerulosclerosis, tubulointerstitial damage, renal interstitial fibrosis, and renal collagen III mRNA expression revealed a significant improvement of all parameters in MWF-6(SHR) compared with MWF (P < 0.05). At 32 wk, MWF but not MWF-6(SHR) demonstrated overt proteinuria (354.6 +/- 37.6 versus 48.8 +/- 13.2; P < 0.0001), whereas serum urea, cholesterol, and triglyceride concentrations were lower and creatinine clearance was higher in MWF-6(SHR) compared with MWF (P < 0.05). Therefore, although albuminuria in MWF is determined by a complex interplay of several QTL, our data demonstrate that genetic exchange of one locus on RNO6 leads to marked suppression of early-onset albuminuria and renal damage in MWF.
Udgivelsesdato: 2007-Jan
Original languageEnglish
JournalJournal of the American Society of Nephrology
Pages (from-to)113-21
Number of pages8
Publication statusPublished - 2007

    Research areas

  • Albuminuria, Animals, Animals, Congenic, Base Sequence, Chromosome Mapping, Crosses, Genetic, DNA Primers, Kidney, Male, Phenotype, Proteinuria, Quantitative Trait Loci, Rats, Rats, Inbred SHR, Rats, Mutant Strains, Rats, Wistar

See relations at Aarhus University Citationformats

ID: 10371019