title: Neurological abnormalities in a knock-in mouse model of Huntington's disease.
abstract: Mice representing precise genetic replicas of Huntington's disease (HD) were made using gene targeting to replace the short CAG repeat of the mouse Huntington's disease gene homolog (HDH:) with CAG repeats within the length range found to cause HD in humans. Mice with alleles of approximately 150 units in length exhibit late-onset behavioral and neuroanatomic abnormalities consistent with HD. These symptoms include a motor task deficit, gait abnormalities, reactive gliosis and the formation of neuronal intranuclear inclusions predominating in the striatum. This model differs from previously described HDH: knock-ins by its method of construction, longer repeat length and more severe phenotype. To our knowledge, this is the first knock-in mouse model of HD to show increased glial fibrillary acidic protein immunoreactivity in the striatum, suggesting that these mice have neuronal injury similar to that found early in the course of HD. These mice will serve as useful reagents in experiments designed to reveal the molecular nature of neuronal dysfunction underlying HD.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Tallaksen-Greene
authors.forename: W M
authors.initials: WM
authors.lastname: Chien
authors.forename: J A
authors.initials: JA
authors.lastname: Cearley
authors.forename: W S
authors.initials: WS
authors.lastname: Jackson
authors.forename: A B
authors.initials: AB
authors.lastname: Crouse
authors.forename: S
authors.initials: S
authors.lastname: Ren
authors.forename: X J
authors.initials: XJ
authors.lastname: Li
authors.forename: R L
authors.initials: RL
authors.lastname: Albin
authors.forename: P J
authors.initials: PJ
authors.lastname: Detloff
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D004195:Disease Models, Animal; D018390:Gene Targeting; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000378:metabolism; D006130:Growth Disorders / Q000235:genetics; D006720:Homozygote; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D007794:Lameness, Animal / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D019680:Trinucleotide Repeat Expansion
chemical_list: D005904:Glial Fibrillary Acidic Protein; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine