RGD Reference Report - Protective effect of female gender on the development of albuminuria in a polygenetic rat model is further enhanced by replacement of a major autosomal QTL. - Rat Genome Database

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Protective effect of female gender on the development of albuminuria in a polygenetic rat model is further enhanced by replacement of a major autosomal QTL.

Authors: Schulz, A  Schlesener, M  Weiss, J  Hansch, J  Wendt, N  Kossmehl, P  Grimm, D  Vetter, R  Kreutz, R 
Citation: Schulz A, etal., Clin Sci (Lond). 2007 Oct 22;.
RGD ID: 1642911
Pubmed: PMID:17953514   (View Abstract at PubMed)
DOI: DOI:10.1042/CS20070300   (Journal Full-text)

Clinical and experimental studies indicate that the progression of renal disease is faster in males than females. These observations are corroborated by a sexual dimorphism observed in the polygenetic Munich Wistar Fromter (MWF) rat model. The age dependent spontaneous progression of increased urinary albumin excretion (UAE) in male MWF is influenced by multiple quantitative trait loci (QTL). In contrast, female MWF develop only a slight increase in UAE, while the role of genetic factors for this phenotype is unknown. Here we show that compared to resistant spontaneously hypertensive rats (SHR) both male and female MWF develop a significant increase in UAE at 24 weeks of age (p<0.0001, respectively), although blood pressures are lower compared to SHR (p<0.0001). UAE is significantly higher in male (7fold) compared to female MWF (162.6+/-15.9 vs. 24.0+/-5.5 mg/24h, p<0.0001) and only male MWF develop significant glomerulosclerosis and tubulointerstitial damage in the kidney (p<0.0001). To test the role of genetic factors for the development of low grade albuminuria in female MWF we analyzed the role of a major UAE QTL on rat chromosome 6. To this end we analyzed a consomic MWF-6 SHR strain in which chromosome 6 from SHR was introgressed into the MWF background. Time course analysis of UAE in females indicated that the mild increase of UAE in MWF was fully suppressed by exchange of rat chromosome 6. Thus, taken together with previous studies in males we show that RNO6 protects against the increase of albuminuria with age in both female and male MWF.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/FubRkbRatAlbuminuria sexual_dimorphismIAGP compared to female MWF/FubRkb strain RGD 
Uae37RatAlbuminuria  IDA  RGD 
MWF/FubRkbRatglomerulosclerosis sexual_dimorphismIAGP compared to female MWF/FubRkb strainRGD 
SHR/FubRkbRathypertension sexual_dimorphismIAGP compared to female SHR/FubRkbRGD 
MWF/FubRkbRatTubulointerstitial Fibrosis  IAGP compared to SHR/FubRkbRGD 
MWF/FubRkbRatTubulointerstitial Fibrosis sexual_dimorphismIAGP compared to female MWF/FubRkb strainRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MWF/FubRkbRatalbuminuria  IAGP females compared to female SHR/FubRkb and female MWF-Chr 6SHR/RkbRGD 
Uae37Ratalbuminuria  IDA  RGD 
MWF-Chr 6SHR/RkbRatdecreased blood urea nitrogen level  IAGP females compared to female MWF/FubRkbRGD 
SHR/FubRkbRatdecreased blood urea nitrogen level  IAGP compared to female MWF/RkbRGD 
SHR/FubRkbRatdecreased circulating creatinine level  IAGP females compared to female MWF/FubRkb and female MWF-Chr 6SHR/RkbRGD 
MWF/FubRkbRatdecreased systemic arterial systolic blood pressure  IAGP compared to SHR/FubRkbRGD 
SHR/FubRkbRatdecreased systemic arterial systolic blood pressure sexual_dimorphismIAGP compared to male SHR/FubRkbRGD 
MWF-Chr 6SHR/RkbRatdecreased urine albumin level sexual_dimorphismIAGP compared to malesRGD 
MWF/FubRkbRatdecreased urine albumin level sexual_dimorphismIAGP compared to male MWF/FubRkbRGD 
MWF/FubRkbRatglomerulosclerosis sexual_dimorphismIAGP compared to female MWF/RkbRGD 
MWF/FubRkbRatincreased blood urea nitrogen level  IAGP females compared to female SHR/FubRkb and female MWF-Chr 6SHR/RkbRGD 
SHR/FubRkbRatincreased heart weight  IAGP females compared to female MWF/FubRkb and female MWF-Chr 6SHR/RkbRGD 
MWF/FubRkbRatincreased hydroxymethylbilane synthase activity  IAGP compared to SHR/FubRkb and MWF-Chr 6SHR/RkbRGD 
SHR/FubRkbRatincreased systemic arterial systolic blood pressure  IAGP compared to MWF/FubRkb more ...RGD 
Uae37Ratincreased urine protein level  IDA  RGD 
MWF/FubRkbRatrenal interstitial fibrosis sexual_dimorphismIAGP males compared to SHR/FubRkb and female MWF/FubRkbRGD 

Objects Annotated

QTLs
Uae37  (Urinary albumin excretion QTL 37)

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

Objects referenced in this article
QTL Uae22 Urinary albumin excretion QTL 22 Rattus norvegicus

Additional Information