RGD Reference Report - Development of overt proteinuria in the Munich Wistar Fromter rat is suppressed by replacement of chromosome 6 in a consomic rat strain. - Rat Genome Database

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

Authors: Schulz, A  Weiss, J  Schlesener, M  Hansch, J  Wehland, M  Wendt, N  Kossmehl, P  Sietmann, A  Grimm, D  Stoll, M  Nyengaard, JR  Kreutz, R 
Citation: Schulz A, etal., J Am Soc Nephrol. 2007 Jan;18(1):113-21. Epub 2006 Dec 13.
RGD ID: 1600609
Pubmed: PMID:17167120   (View Abstract at PubMed)
DOI: DOI:10.1681/ASN.2006030206   (Journal Full-text)

In a cross between the Munich Wistar Fromter (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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/FubRkbRatAlbuminuria MODEL: spontaneousIAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/FubRkbRatalbuminuria  IAGP compared to SHR/FubRkb strainRGD 
MWF-Chr 6SHR/RkbRatdecreased heart weight  IAGP compared to SHR/FubRkb strainRGD 
MWF/FubRkbRatdecreased heart weight  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 
MWF/FubRkbRatdecreased kidney weight  IAGP compared to SHR/FubRkb strainRGD 
MWF/FubRkbRatdecreased renal glomerulus number  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 
MWF-Chr 6SHR/RkbRatdecreased systemic arterial systolic blood pressure  IAGP compared to SHR/FubRkb strainRGD 
MWF/FubRkbRatdecreased systemic arterial systolic blood pressure  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 
MWF/FubRkbRatincreased blood urea nitrogen level  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 
MWF/FubRkbRatincreased circulating cholesterol level  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/Rkb strainsRGD 
MWF-Chr 6SHR/RkbRatincreased circulating triglyceride level  IAGP compared to SHR/FubRkb strainRGD 
MWF/FubRkbRatincreased circulating triglyceride level  IAGP compared to SHR/FubRkb strainRGD 

Objects Annotated

Strains
MWF-Chr 6SHR/Rkb  (NA)
MWF/FubRkb  (Munich Wistar Fromter)

Objects referenced in this article
Strain SHR/FubRkb null Rattus norvegicus
QTL Uae22 Urinary albumin excretion QTL 22 Rattus norvegicus

Additional Information