Mapping and sequencing rat dishevelled-1: a candidate gene for cerebral ischaemic insult in a rat model of stroke

R. P. De Lange, K. Burr, J. S. Clark, C. D. Negrin, M. J. Brosnan, David Malcolm St Clair, A. F. Dominiczak, Duncan James Shaw

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A quantitative trait locus on chromosome 5 in the rat is linked to sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). The genes encoding atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) that map to this location have been excluded as candidate genes. We examined dishevelled-1 (DVL-1) as a further candidate gene. DVL-1 had not yet been identified in the rat, but Anp, Bnp, and DVL-1 map to the homologous regions of the rat chromosome 5 quantitative trait locus in both mice and man. Furthermore, DVL-1 is involved in the Notch signalling system, which plays a role in the disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the symptoms of which include ischaemic stroke. We show with radiation hybrid mapping that rat DVL-1 indeed maps to chromosome 5, where it is positioned immediately next to microsatellite marker D5Rat49. We sequenced the complete coding sequence and a large part of the intronic genomic sequence for the SHRSP strain and its reference Wistar-Kyoto strain. The DVL-1 sequence in the two strains was identical. Our results essentially exclude the DVL-1 gene as the cause for sensitivity to cerebral ischaemic insult in this rat model of stroke.

Original languageEnglish
Pages (from-to)99-106
Number of pages7
JournalNeurogenetics
Volume3
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • genomic structure
  • chromosomal location
  • dishevelled
  • hypertension
  • rat
  • SPONTANEOUSLY HYPERTENSIVE RATS
  • NOTCH3 MUTATIONS
  • POLARITY GENE
  • PRONE
  • SENSITIVITY
  • CADASIL
  • TRAIT

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