title: Chromosomal mapping of quantitative trait loci controlling elastin content in rat aorta.
abstract: Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Jacques
authors.initials: J
authors.lastname: Behmoaras
authors.forename: Karène
authors.initials: K
authors.lastname: Argoud
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wilder
authors.forename: Christelle
authors.initials: C
authors.lastname: Pradines
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Bihoreau
authors.forename: Mary
authors.initials: M
authors.lastname: Osborne-Pellegrin
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Jacob
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002874:Chromosome Mapping; D004549:Elastin / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D008040:Genetic Linkage; D006824:Hybridization, Genetic; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains
chemical_list: D004549:Elastin