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.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

QTLs
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)

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

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

Additional Information