title: A mouse model of heritable cerebrovascular disease.
abstract: The study of animal models of heritable cerebrovascular diseases can improve our understanding of disease mechanisms, identify candidate genes for related human disorders, and provide experimental models for preclinical trials. Here we describe a spontaneous mouse mutation that results in reproducible, adult-onset, progressive, focal ischemia in the brain. The pathology is not the result of hemorrhage, embolism, or an anatomical abnormality in the cerebral vasculature. The mutation maps as a single site recessive locus to mouse Chromosome 9 at 105 Mb, a region of shared synteny with human chromosome 3q22. The genetic interval, defined by recombination mapping, contains seven protein-coding genes and one processed transcript, none of which are changed in their expression level, splicing, or sequence in affected mice. Targeted resequencing of the entire interval did not reveal any provocative changes; thus, the causative molecular lesion has not been identified.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sproule
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
authors.forename: Jill
authors.initials: J
authors.lastname: Wentzell
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Robert W
authors.initials: RW
authors.lastname: Burgess
mesh_terms: D000818:Animals; D001483:Base Sequence; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology*; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D014057:Tomography, X-Ray Computed / Q000379:methods