Faculty Collaboration Database

Genetically hypertensive Brown Norway congenic rat strains suggest intermediate traits underlying genetic hypertension. Croat Med J 2008 Oct;49(5):586-99

Date

10/18/2008

Pubmed ID

18925692

Pubmed Central ID

PMC2582351

DOI

10.3325/cmj.2008.5.586

Scopus ID

2-s2.0-57149093204 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

AIM: To determine the independent and combined effects of three quantitative trait loci (QTL) for blood pressure in the Genetically Hypertensive (GH/Omr) rat by generating and characterizing single and combined congenic strains that have QTL on rat chromosomes (RNO) 2, 6, and 18 from the GH rat introduced into a hypertension resistant Brown Norway (BN) background.

METHODS: Linkage analysis and QTL identification (genome wide QTL scan) were performed with MapMaker/EXP to build the genetic maps and MapMaker/QTL for linking the phenotypes to the genetic map. The congenic strains were derived using marker-assisted selection strategy from a single male F1 offspring of an intercross between the male GH/Omr and female BN/Elh, followed by 10 generations of selective backcrossing to the female BN progenitor strain. Single congenic strains generated were BN.GH-(D2Rat22-D2Mgh11)/Mcwi (BN.GH2); BN.GH-(D6Mit12-D6Rat15)/Mcwi (BN.GH6); and BN.GH-(D18Rat41-D18Mgh4)/Mcwi (BN.GH18). Blood pressure measurements were obtained either via a catheter placed in the femoral artery or by radiotelemetry. Responses to angiotensin II (ANGII), norepinephrine (NE), and baroreceptor sensitivity were measured in the single congenics.

RESULTS: Transferring one or more QTL from the hypertensive GH into normotensive BN strain was not sufficient to cause hypertension in any of the developed congenic strains. There were no differences between the parental and congenic strains in their response to NE. However, BN.GH18 rats revealed significantly lower baroreceptor sensitivity (beta=-1.25-/+0.17), whereas BN.GH2 (beta=0.66-/+0.09) and BN.GH18 (beta=0.71-/+0.07) had significantly decreased responses to ANGII from those observed in the BN (beta=0.88-/+0.08).

CONCLUSION: The failure to alter blood pressure levels by introducing the hypertensive QTL from the GH into the hypertension resistant BN background suggests that the QTL effects are genome background-dependent in the GH rat. BN.GH2 and BN.GH18 rats reveal significant differences in response to ANGII and impaired baroreflex sensitivity, suggesting that we may have captured a locus responsible for the genetic control of baroreceptor sensitivity, which would be considered an intermediate phenotype of blood pressure.

Author List

Bilusić M, Moreno C, Barreto NE, Tschannen MR, Harris EL, Porteous WK, Thompson CM, Grigor MR, Weder A, Boerwinkle E, Hunt SC, Curb JD, Jacob HJ, Kwitek AE

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Animals, Congenic
Blood Pressure
Disease Models, Animal
Female
Genetic Linkage
Genetic Markers
Hypertension
Male
Phenotype
Pressoreceptors
Quantitative Trait Loci
Rats
Rats, Inbred BN
Risk Factors