RGD Reference Report - Isolation of a Chromosome 1 Region Affecting Blood Pressure and Vascular Disease Traits in the Stroke-Prone Rat Model. - Rat Genome Database

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Isolation of a Chromosome 1 Region Affecting Blood Pressure and Vascular Disease Traits in the Stroke-Prone Rat Model.

Authors: Kato, N  Nabika, T  Liang, YQ  Mashimo, T  Inomata, H  Watanabe, T  Yanai, K  Yamori, Y  Yazaki, Y  Sasazuki, T 
Citation: Kato N, etal., Hypertension 2003 Dec;42(6):1191-7. Epub 2003 Nov 17.
RGD ID: 730283
Pubmed: PMID:14623828   (View Abstract at PubMed)
DOI: DOI:10.1161/01.HYP.0000103161.27190.67   (Journal Full-text)

Recently, a genome-wide screen has shown a major quantitative trait locus (QTL) for a stroke-associated phenotype on rat chromosome 1 (RNO1) independent of QTL for blood pressure (BP) in the stroke-prone spontaneously hypertensive rat (SHRSP) of a Heidelberg colony. However, it remains to be elucidated whether these observations reflect the existence of different genes predisposing to each of the disorders. To address this issue, we performed comprehensive approaches in a Japanese colony, Izm, as follows. First, we undertook genome-wide searches in F1(SHRSP/IzmxWKY/Izm)xSHRSP/Izm back-cross (n=63) to pursue a causal relation between hypertension and stroke. Although the strongest linkage to BP (LOD score of 3.4) was identified on RNO1, its relevance to stroke was not supported in the F1 back-cross studied. Second, we also investigated linkage to BP in F2 progeny (n=175) involving the stroke-resistant (or normal) spontaneously hypertensive rat (SHR). In F2 studies of SHR/Izm, this locus did not appear to constitute a principal BP QTL. Third, we constructed congenic animals with detailed phenotype characterization. Transfer of a chromosomal fragment between markers Klk1 and D1Rat116 from WKY/Izm onto the SHRSP/Izm background lowered systolic BP by 20 to 80 mm Hg, prevented development of apparent stroke, and exaggerated impaired glucose tolerance. In conclusion, we have successfully isolated an RNO1 region affecting BP, stroke, and glucose tolerance in SHRSP/Izm-derived congenic rats. The size of the introgressed region is large, but our novel congenic strain should help delineate complex, genetic impairments underlying BP and associated vascular disease phenotypes.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp154Rathypertension  IDA  RGD 
SHRSP/IzmRathypertension MODEL: spontaneousIAGP compared to control strain WKY/Izm more ...RGD 
WKY/IzmRathypertension MODEL: controlIAGP compared to spontaneously hypertensive strain SHRSP/IzmRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatabnormal systemic arterial blood pressure  IAGP  RGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatdecreased body weight  IAGP compared to SHRSP/Izm and in maleRGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatdecreased heart weight  IAGP compared to SHRSP/Izm and in femaleRGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatdecreased susceptibility to hypertension  IAGP compared to SHRSP/IzmRGD 
WKY/IzmRatdecreased susceptibility to hypertension  IAGP compared to SHRSP/IzmRGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatdecreased susceptibility to ischemic brain injury  IAGPcontrolled sodium content drinking watercompared to SHRSP/IzmRGD 
Bp154Ratdecreased systemic arterial blood pressure  IAGP  RGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatdecreased systemic arterial systolic blood pressure  IAGP compared to SHRSP/IzmRGD 
WKY/IzmRatdecreased systemic arterial systolic blood pressure  IAGP compared to SHRSP/IzmRGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatimpaired glucose tolerance  IAGP compared to SHRSP/Izm and MMO:0000326RGD 
WKY/IzmRatimpaired glucose tolerance  IAGP compared to SHRSP/Izm and MMO:0000326RGD 
SHRSP.WKY-(Klk1-D1Rat116)/IzmRatincreased circulating glucose level  IAGP compared to SHRSP/Izm and in femaleRGD 
SHRSP/IzmRatincreased susceptibility to hypertension  IAGP compared to control strain WKY/Izm more ...RGD 
SHRSP/IzmRatincreased susceptibility to ischemic brain injury  IAGPcontrolled sodium content drinking watercompared to control strain WKY/IzmRGD 
SHRSP/IzmRatincreased systemic arterial systolic blood pressure  IAGP compared to control strain WKY/Izm more ...RGD 
SHRSP/IzmRatsalt-sensitive hypertension susceptibilityIAGPcontrolled sodium content drinking watercompared to control strain WKY/IzmRGD 

Objects Annotated

QTLs
Bp154  (Blood pressure QTL 154)

Strains
SHRSP.WKY-(Klk1-D1Rat116)/Izm  (NA)
SHRSP/Izm  (NA)
WKY/Izm  (Wistar-Kyoto)


Additional Information