title: Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.
abstract: The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.
authors.affiliation: Institute of Biology, First Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Kren
authors.forename: M
authors.initials: M
authors.lastname: Pravenec
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: D
authors.initials: D
authors.lastname: Krenova
authors.forename: J M
authors.initials: JM
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Merriouns
authors.forename: A
authors.initials: A
authors.lastname: Wong
authors.forename: E
authors.initials: E
authors.lastname: St Lezin
authors.forename: D
authors.initials: D
authors.lastname: Lau
authors.forename: C
authors.initials: C
authors.lastname: Szpirer
authors.forename: J
authors.initials: J
authors.lastname: Szpirer
authors.forename: T W
authors.initials: TW
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D005838:Genotype; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D013045:Species Specificity