RGD Reference Report - A major gene locus links early onset albuminuria with renal interstitial fibrosis in the MWF rat with polygenetic albuminuria. - Rat Genome Database

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A major gene locus links early onset albuminuria with renal interstitial fibrosis in the MWF rat with polygenetic albuminuria.

Authors: Schulz, A  Standke, D  Kovacevic, L  Mostler, M  Kossmehl, P  Stoll, M  Kreutz, R 
Citation: Schulz A, etal., J Am Soc Nephrol 2003 Dec;14(12):3081-9.
RGD ID: 730279
Pubmed: PMID:14638907   (View Abstract at PubMed)

The development of renal interstitial fibrosis (RIF) represents an important step in the progression of chronic proteinuric nephropathies. The Munich Wistar Fromter (MWF) rat represents a valuable model to study the progression in proteinuric renal disease. MWF animals demonstrate a significant increase of urinary albumin excretion (UAE) and RIF compared with the spontaneously hypertensive rat (SHR) with low UAE. The aim of this study was to analyze the genetic basis and the relation between UAE and RIF by genetic linkage and quantitative trait loci (QTL) mapping analysis. The authors generated a backcross population between MWF and SHR including 215 male animals. UAE was determined in young backcross animals at 8 wk, and at 14 and 24 wk of age, respectively. RIF was evaluated by Sirius red staining of kidney sections and quantified by computer-assisted image analysis at 24 wk. Total genome scan analysis identified in total eight QTL linked to UAE and a major locus on chromosome 6. At this locus, homozygosity for the MWF allele exhibited a strong effect on UAE levels (threefold elevation) and displayed significant linkage already at 8 wk (logarithm of odds [LOD] = 4.3) with increasing significance at 14 and 24 wk (LOD = 7.8 and 10.1, respectively). In addition, this was the only QTL that was linked to the amount of RIF (P = 0.0009, LOD = 2.4). These data establish a genetic link between early onset albuminuria and progression of RIF at the QTL on RNO6. This study demonstrates the power of genetic linkage analysis for the dissection of physiologic pathways involved in renal disease progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Glom4RatAlbuminuria  IAGP  RGD 
Glom5RatAlbuminuria  IAGP  RGD 
Glom6RatAlbuminuria  IAGP  RGD 
Glom7RatAlbuminuria  IAGP  RGD 
Glom8RatAlbuminuria  IAGP  RGD 
MWF/FubRatAlbuminuria MODEL: spontaneousIAGP compared to SHR/Fub strainRGD 
Uae20RatAlbuminuria  IAGP  RGD 
Uae21RatAlbuminuria  IAGP  RGD 
Uae22RatAlbuminuria  IAGP  RGD 
Uae23RatAlbuminuria  IAGP  RGD 
Uae24RatAlbuminuria  IAGP  RGD 
Uae25RatAlbuminuria  IAGP  RGD 
Uae26RatAlbuminuria  IAGP  RGD 
Uae27RatAlbuminuria  IAGP  RGD 
Glom4Ratproteinuria  IAGP  RGD 
Glom5Ratproteinuria  IAGP  RGD 
Glom6Ratproteinuria  IAGP  RGD 
Pur3Ratproteinuria  IAGP  RGD 
MWF/FubRatTubulointerstitial Fibrosis MODEL: spontaneousIAGP compared to SHR/Fub strainRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Glom4Ratabnormal renal glomerulus morphology  IAGP  RGD 
Glom5Ratabnormal renal glomerulus morphology  IAGP  RGD 
Glom6Ratabnormal renal glomerulus morphology  IAGP  RGD 
Glom7Ratabnormal renal glomerulus morphology  IAGP  RGD 
Glom8Ratabnormal renal glomerulus morphology  IAGP  RGD 
MWF/FubRatabnormal renal glomerulus morphology  IAGP compared to SHR/Fub strainRGD 
Uae20Ratalbuminuria  IAGP  RGD 
Uae21Ratalbuminuria  IAGP  RGD 
Uae22Ratalbuminuria  IAGP  RGD 
Uae23Ratalbuminuria  IAGP  RGD 
Uae24Ratalbuminuria  IAGP  RGD 
Uae25Ratalbuminuria  IAGP  RGD 
Uae26Ratalbuminuria  IAGP  RGD 
Uae27Ratalbuminuria  IAGP  RGD 
MWF/FubRatdecreased body weight  IAGP compared to SHR/Fub strainRGD 
MWF/FubRatdecreased kidney weight  IAGP compared to SHR/Fub strainRGD 
Pur3Ratincreased urine protein level  IAGP  RGD 
MWF/FubRatrenal interstitial fibrosis  IAGP compared to SHR/Fub strainRGD 

Objects Annotated

Glom4  (Glomerulus QTL 4)
Glom5  (Glomerulus QTL 5)
Glom6  (Glomerulus QTL 6)
Glom7  (Glomerulus QTL 7)
Glom8  (Glomerulus QTL 8)
Pur3  (Proteinuria QTL 3)
Uae20  (Urinary albumin excretion QTL 20)
Uae21  (Urinary albumin excretion QTL 21)
Uae22  (Urinary albumin excretion QTL 22)
Uae23  (Urinary albumin excretion QTL 23)
Uae24  (Urinary albumin excretion QTL 24)
Uae25  (Urinary albumin excretion QTL 25)
Uae26  (Urinary albumin excretion QTL 26)
Uae27  (Urinary albumin excretion QTL 27)

MWF/Fub  (Munich Wistar Fromter)
SHR/Fub  (NA)

Objects referenced in this article
Strain MWF/FubRkb Munich Wistar Fromter Rattus norvegicus

Additional Information