RGD Reference Report - Genetic dissection of increased urinary albumin excretion in the munich wistar fromter rat. - Rat Genome Database

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Genetic dissection of increased urinary albumin excretion in the munich wistar fromter rat.

Authors: Schulz, A  Litfin, A  Kossmehl, P  Kreutz, R 
Citation: Schulz A, etal., J Am Soc Nephrol 2002 Nov;13(11):2706-14.
RGD ID: 634618
Pubmed: (View Article at PubMed) PMID:12397040

An elevated urinary albumin excretion (UAE) is a risk factor for the development of chronic nephropathy and for cardiovascular mortality. The Munich Wistar Fromter (MWF) rat represents a genetic model that develops spontaneously mild hypertension and a 142-fold increased UAE compared with normal Lewis rats at 14 wk of age. The genetic basis of UAE in male MWF was analyzed in relation to BP by using a quantitative trait (QTL) mapping strategy. F1-hybrids generated from a cross between MWF and Lewis rats showed normal UAE rates similar to Lewis. A backcross strategy including 213 animals was therefore used. To account for age-of-onset effects, UAE was determined in young backcross animals at 8 wk and in adult animals at 14 and 24 wk of age, respectively. Total genome scan analysis identified three QTL with significant linkage to UAE and one QTL with suggestive linkage to UAE. These loci showed no linkage to BP, and BP explained only 2% of the total variance of UAE. Homozygosity for the MWF allele accounted for a similar mean increase in UAE in adult backcross animals at each UAE QTL. When single gene effects were analyzed, only one UAE QTL led to a significant increase in UAE. Early onset of albuminuria and a considerable increase of UAE in adult animals required homozygosity at three loci at least. This study demonstrates the polygenetic recessive determination of increased UAE by a set of genes that are unlinked to BP.

Annotation

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Objects Annotated

QTLs
Bp145  (Blood pressure QTL 145)
Bp146  (Blood pressure QTL 146)
Bp147  (Blood pressure QTL 147)
Glom1  (Glomerulus QTL 1)
Glom2  (Glomerulus QTL 2)
Glom3  (Glomerulus QTL 3)
Uae1  (Urinary albumin excretion QTL 1)
Uae2  (Urinary albumin excretion QTL 2)
Uae3  (Urinary albumin excretion QTL 3)
Uae4  (Urinary albumin excretion QTL 4)

Strains
MWF/FubRkb  (Munich Wistar Fromter)

Objects referenced in this article
Gene Gne glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase Rattus norvegicus
Strain LEW/Rkb null Rattus norvegicus

Additional Information