RGD Reference Report - Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus. - Rat Genome Database

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Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus.

Authors: Jeffs, B  Clark, JS  Anderson, NH  Gratton, J  Brosnan, MJ  Gauguier, D  Reid, JL  Macrae, IM  Dominiczak, AF 
Citation: Jeffs B, etal., Nat Genet 1997 Aug;16(4):364-7
RGD ID: 61056
Pubmed: PMID:9241273   (View Abstract at PubMed)
DOI: DOI:10.1038/ng0897-364   (Journal Full-text)

Ischaemic stroke is a complex disorder caused by a combination of genetic and environmental factors. Clinical and epidemiological studies have provided strong evidence for genetic influences in the development of human stroke and several mendelian traits featuring stroke have been described. The genetic analysis of the non-mendelian, common ischaemic stroke in humans is hindered by the late onset of the disease and the mode of inheritance, which is complex, polygenic and multifactorial. An important approach to the study of such polygenic diseases is the use of appropriate animal models in which individual contributing factors can be recognized and analysed. The spontaneously hypertensive stroke-prone rat (SHRSP) is an experimental model of stroke characterized by a high frequency of spontaneous strokes as well as an increased sensitivity to experimentally induced focal cerebral ischaemia. Rubattu et al. performed a genomewide screen in an F2 cross obtained by mating SHRSP and SHR, in which latency to stroke on Japanese rat diet was used as a phenotype. This study identified three major quantitative trait loci (QTLs), STR-1-3. Of these, STR-2 and 3 conferred a protective effect against stroke in the presence of SHRSP alleles and STR-2 co-localized with the genes encoding for atrial natriuretic and brain natriuretic factors. Our investigation was designed to identify the genetic component responsible for large infarct volumes in the SHRSP in response to a focal ischaemic insult by performance of a genome scan in an F2 cross derived from the SHRSP and the normotensive reference strain, WKY rat. We identified a highly significant QTL on rat chromosome 5 with a lod score of 16.6 which accounts for 67% of the total variance, co-localizes with the genes encoding atrial and brain natriuretic factor and is blood pressure independent.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp49Ratbrain infarction  IDA  RGD 
SHRSP/GcrcRatbrain ischemia MODEL: inducedIAGPmiddle cerebral artery occlusioncompared to WKY/GcrcRGD 
Bp49Rathypertension  IDA  RGD 
SHRSP/GcrcRatStroke MODEL: inducedIAGPmiddle cerebral artery occlusioncompared to WKY/GcrcRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp49Ratincreased cerebral infarct size  IDA  RGD 
Bp49Ratincreased systemic arterial blood pressure  IAGP  RGD 
Objects Annotated

QTLs
Bp49  (Blood pressure QTL 49)

Strains
SHRSP  (Spontaneously Hypertensive Rat, Stroke Prone)
SHRSP/Gcrc  (Spontaneously hypertensive rat, stroke prone)
WKY  (NA)

Objects referenced in this article
Marker D5Mit9 D5Mit9 Rattus norvegicus
Marker D5Wox4 D5Wox4 Rattus norvegicus
Gene Nppa natriuretic peptide A Rattus norvegicus
QTL Sprol1 Serum protein level QTL 1 Rattus norvegicus

Additional Information