Izvorni znanstveni članak
Genetically Hypertensive Brown Norway Congenic Rat Strains Suggest Intermediate Traits Underlying Genetic Hypertension
Marijo Bilušić
; Trinitas Hospital, Department of Internal Medicine, Seton Hall University, Elizabeth, NJ, USA
Carol Moreno
; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wis, USA
Nadia E. Barreto
; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wis, USA
Michael R. Tschannen
; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wis, USA
Eugenie L. Harris
; Childrens Hospital of Wisconsin, Milwaukee, Wis, USA
William K. Porteous
; Childrens Hospital of Wisconsin, Milwaukee, Wis, USA
Caryn M. Thompson
; Department of Bioinformatics and Biostatistics, University of Louisville, Ky, USA
Murray R. Grigor
; Department of Biochemistry, University of Otago, New Zealand
Alan Weder
; University of Michigan Hospital, Ann Arbor, Mich, USA
Eric Boerwinkle
; Human Genetics Center, University of Texas, Houston, Tex, USA
Steven C. Hunt
; University of Utah, Salt Lake City, Utah, USA
J. David Curb
; The Honolulu Hearth Program Pacific Health Research Institute, Honolulu, Hawaii, USA
Howard J. Jacob
; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wis, USA
Anne E. Kwitek
; Department of Internal Medicine, University of Iowa, Iowa City, USA
Sažetak
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 in the single and combined congenics. 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
(β = -1.25 ± 0.17), whereas BN.GH2 (β = 0.66 ± 0.09) and BN.GH18
(β = 0.71 ± 0.07) had significantly decreased responses to ANGII from
those observed in the BN (β = 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 backgrounddependent
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.
Ključne riječi
Genetically Hypertensive rat; congenic; angiotensin II, baroreceptor reflex; QTL; hypertension
Hrčak ID:
29272
URI
Datum izdavanja:
15.10.2008.
Posjeta: 918 *