1. Croat Med J. 2008 Oct;49(5):586-99.
Genetically hypertensive Brown Norway congenic rat strains suggest intermediate
traits underlying genetic hypertension.
Bilusić M(1), 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 information:
(1)Trinitas Hospital, Department of Internal Medicine, Seton Hall University,
Elizabeth, NJ, USA.
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.
PMCID: PMC2582351
PMID: 18925692 [PubMed - indexed for MEDLINE]
PUBMED: 18925692
Find other GeneSets from this publication
GeneWeaver