RGD Reference Report - Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats. - Rat Genome Database

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Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats.

Authors: Yao, H  Cui, ZH  Masuda, J  Nabika, T 
Citation: Yao H, etal., Physiol Genomics. 2007 Feb 27;.
RGD ID: 1600255
Pubmed: PMID:17327494   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00149.2006   (Journal Full-text)

A genome-wide screen found a blood pressure quantitative trait locus (QTL) on rat chromosome 1 in stroke-prone spontaneously hypertensive rats of a Japanese colony (SHRSP/Izm). In the present study, we investigated the effects of congenic removal of this QTL from SHRSP/Izm on infarct size produced by middle cerebral artery (MCA) occlusion. To establish the congenic strain (SHRSPwch1.0), the blood pressure QTL was introgressed from Wistar-Kyoto/Izm to SHRSP/Izm by repeated backcrossing. Male SHRSP/Izm (10-12 weeks old [young adult] n=8, 5 months old [adult] n=17) and SHRSPwch1.0 (young adult n=7, adult n=15) were randomly assigned to distal MCA occlusion. Resting mean arterial blood pressure (MABP) was 212+/-23 mmHg in adult SHRSPwch1.0, which was significantly lower than 241+/-22 mmHg in SHRSP/Izm. Infarct volume in the congenic rats was significantly decreased compared with that in SHRSP/Izm (66.4+/-21.5 mm(3) vs. 103.4+/-24.8 mm(3)). Cerebral blood flow, determined at collaterally-perfused cortex with laser-Doppler flowmetry after MCA occlusion, was significantly greater in adult SHRSPwch1.0 compared with CBF in adult SHRSP/Izm. In young adult rats, there were no significant differences in MABP or in infarct volume between SHRSPwch1.0 and SHRSP/Izm. The congenic removal of a blood pressure QTL lowered blood pressure and caused a substantial reduction in infarct volume (-36%) with increased collateral CBF after MCA occlusion in the congenic rat. We demonstrated for the first time that the congenic strategy is useful to investigate the effects of genetic hypertension on focal ischemia or stroke. Key words: genetics, stroke, cerebral ischemia, focal, hypertension, models, animal.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp298RatHypotension  IDA  RGD 
SHRSP/IzmRatmiddle cerebral artery infarction MODEL: inducedIAGPmiddle cerebral artery occlusioncompared to congenic SHRSP.WKY-(D1Wox29-D1Arb21)/Izm and with ageRGD 
Bp298RatMyocardial Ischemia  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SHRSP.WKY-(D1Wox29-D1Arb21)/IzmRatdecreased cerebral infarct size  IAGPmiddle cerebral artery occlusioncompared to SHRSP/IzmRGD 
Bp298Ratdecreased mean systemic arterial blood pressure  IDA  RGD 
SHRSP.WKY-(D1Wox29-D1Arb21)/IzmRatdecreased mean systemic arterial blood pressure  IAGP compared to SHRSP/IzmRGD 
SHRSP.WKY-(D1Wox29-D1Arb21)/IzmRatdecreased susceptibility to ischemic brain injury  IAGPmiddle cerebral artery occlusioncompared to SHRSP/IzmRGD 
SHRSP/IzmRatincreased cerebral infarct size severityIAGPmiddle cerebral artery occlusioncompared to congenic SHRSP.WKY-D1Wox29-D1Arb21/Izm and with ageRGD 
SHRSP/IzmRatincreased mean systemic arterial blood pressure severityIAGP compared to congenic SHRSP.WKY-D1Wox29-D1Arb21/Izm and with ageRGD 
SHRSP/IzmRatincreased susceptibility to ischemic brain injury severityIAGPmiddle cerebral artery occlusioncompared to congenic SHRSP.WKY-D1Wox29-D1Arb21/Izm and with ageRGD 

Objects Annotated

QTLs
Bp298  (Blood pressure QTL 298)

Objects referenced in this article
Strain WKY.SHRSP-(D1Wox29-D1Arb21)/Izm null Rattus norvegicus

Additional Information