title: A gene-targeted mouse model for chorea-acanthocytosis.
abstract: Chorea-acanthocytosis (CHAC) is a hereditary neurodegenerative disorder with autosomal recessive transmission, in which selective degeneration of striatum has been reported in brain pathology. Clinically, CHAC shows Huntington's disease-like neuropsychiatric symptoms and red blood cell acanthocytosis. Recently, we identified the gene, CHAC, encoding a novel protein, chorein, in which a deletion mutation was found in Japanese families with CHAC. In the present study, we have identified the mouse CHAC cDNA sequence and the exon-intron structures of the gene and produced a CHAC model mouse introducing no. 60-61 exon deletion corresponding to a human disease mutation by a gene-targeting technique. The mice began to show acanthocytosis and motor disturbance in old age. In behavioral observations, locomotor activity was significantly decreased and the contact time at social interaction test was decreased significantly in the model mice. In the brain pathology, many apoptotic cells were observed in the striatum of the mutant mice. In neurochemical determinations, the dopamine metabolite, homovanillic acid, concentration decreased significantly in the portion including the midbrain of the mutant mice. These findings are consistent with the human results reported elsewhere and indicate that the CHAC model mice showed a mild phenotype with late adult onset. The CHAC model mouse therefore provides a good model system to study the human disease.
authors.affiliation: Department of Psychiatry, Kagoshima University Graduate School of Medical and Ental Sciences, Kagoshima, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tomemori
authors.forename: Mio
authors.initials: M
authors.lastname: Ichiba
authors.forename: Akira
authors.initials: A
authors.lastname: Kusumoto
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizuno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Shinji
authors.initials: S
authors.lastname: Muroya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Motoya
authors.initials: M
authors.lastname: Katsuki
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
mesh_terms: D000050:Acanthocytes / Q000473:pathology; D000818:Animals; D002819:Chorea / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D013577:Syndrome; D033921:Vesicular Transport Proteins
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D011506:Proteins; C429654:VPS13A protein, human; D033921:Vesicular Transport Proteins; C497828:Vps13a protein, mouse