RGD Reference Report - Genetically Hypertensive Brown Norway congenic rat strains suggest intermediate traits underlying genetic hypertension. - Rat Genome Database

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Genetically Hypertensive Brown Norway congenic rat strains suggest intermediate traits underlying genetic hypertension.

Authors: Bilusic, 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 
Citation: Bilusic M, etal., Croat Med J. 2008 Oct;49(5):586-99.
RGD ID: 2301936
Pubmed: PMID:18925692   (View Abstract at PubMed)
PMCID: PMC2582351   (View Article at PubMed Central)

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.



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RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp322Rathypertension  IAGP  RGD 
Bp323Rathypertension  IAGP  RGD 
Bp324Rathypertension  IAGP  RGD 
Bp325Rathypertension  IAGP  RGD 
Cm71Rathypertension  IAGP  RGD 
Cm72Rathypertension  IAGP  RGD 
Cm73Rathypertension  IAGP  RGD 
GH/OmrRathypertension  IAGP  RGD 
GH/OmrRatLeft Ventricular Hypertrophy  IAGP associated with hypertensionRGD 
Bw81Ratobesity  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Objects Annotated

QTLs
Bp322  (Blood pressure QTL 322)
Bp323  (Blood pressure QTL 323)
Bp324  (Blood pressure QTL 324)
Bp325  (Blood pressure QTL 325)
Bw81  (Body weight QTL 81)
Cm71  (Cardiac mass QTL 71)
Cm72  (Cardiac mass QTL 72)
Cm73  (Cardiac mass QTL 73)

Strains
BN.GH-(D18Rat41-D18Mgh4)/Mcwi  (NA)
BN.GH-(D2Rat22-D2Mgh11)/Mcwi  (NA)
BN/Elh  (NA)
GH/Omr  (Genetically Hypertensive)

Objects referenced in this article
Strain BN.GH-(D2Rat22-D2Mgh11)(D18Rat41-D18Mgh4)/Mcwi null Rattus norvegicus
Strain BN.GH-(D2Rat22-D2Mgh11)(D6Mit12-D6Rat15)(D18Rat41-D18Mgh4)/Mcwi null Rattus norvegicus
Strain BN.GH-(D2Rat22-D2Mgh11)(D6Mit12-D6Rat15)/Mcwi null Rattus norvegicus
Strain BN.GH-(D6Mit12-D6Rat15)(D18Rat41-D18Mgh4)/Mcwi null Rattus norvegicus
Strain BN.GH-(D6Mit12-D6Rat15)/Mcwi null Rattus norvegicus

Additional Information