Document Detail


Genetic dissection of increased urinary albumin excretion in the munich wistar frömter rat.
MedLine Citation:
PMID:  12397040     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An elevated urinary albumin excretion (UAE) is a risk factor for the development of chronic nephropathy and for cardiovascular mortality. The Munich Wistar Frömter (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.
Authors:
Angela Schulz; Andre Litfin; Peter Kossmehl; Reinhold Kreutz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  13     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-24     Completed Date:  2003-04-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2706-14     Citation Subset:  IM    
Affiliation:
Institut für Klinische Pharmakologie und Toxikologie and Medizinische Klinik IV Nephrologie, Universitätsklinikum Benjamin Franklin Hospital, Freie Universität Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Albuminuria / genetics*,  pathology,  physiopathology
Animals
Blood Pressure / physiology
Chromosome Segregation
Crosses, Genetic
Hypertension / genetics
Kidney Glomerulus / pathology
Linkage (Genetics)
Male
Phenotype
Proteinuria / genetics
Quantitative Trait Loci
Rats
Rats, Inbred Lew / genetics
Rats, Wistar / genetics
Reference Values

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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