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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
Volume18
Issue1
Pages (from-to)113-21
Number of pages8
ISSN1046-6673
DOIs
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

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