title: Behavioral abnormalities of Zic1 and Zic2 mutant mice: implications as models for human neurological disorders.
abstract: Zic1 and Zic2 encode closely related zinc finger proteins expressed in dorsal neural tube and its derivatives. In previous studies, we showed that the homozygous Zic1 null mutation (Zic1-/-) results in cerebellar malformation with severe ataxia and that holoprosencephaly and spina bifida occur in homozygotes for Zic2 knockdown mutation (Zic2kd/kd). Since human ZIC2 haploinsufficiency is a cause of holoprosencephaly, the Zic2kd/kd mice are regarded as an animal model for holoprosencephaly in humans. In this study, the behavioral characteristics of the Zic1 and Zic2 mutant mice were investigated in heterozygotes (Zic1-/+ or Zic2kd/+), and significant abnormalities were found in the hanging, spontaneous locomotor activity, stationary rod (Zic1-/+), acoustic startle response, and prepulse inhibition tests (Zic2kd/+). The abnormalities in the Zic1-/+ mice may be explained in part by the hypotonia caused by hypoplasia of the cerebellar anterior vermis, and these mice are regarded as a model of Joubert syndrome. In contrast, the sensorimotor gating abnormality in the Zic2kd/+ mice may be attributable to the presumed abnormality in the dorsomedial forebrain, which was strongly affected in the Zic2kd/kd mice. Zic2kd/+ mice can serve as a model for diseases involving sensorimotor gating abnormalities, such as schizophrenia.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co. Ltd., Tsukuba-shi, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogura
authors.forename: J
authors.initials: J
authors.lastname: Aruga
authors.forename: K
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000002:abnormalities; D004195:Disease Models, Animal; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D008957:Models, Genetic; D009123:Muscle Hypotonia / Q000235:genetics*; D009687:Nuclear Proteins; D012559:Schizophrenia / Q000235:genetics*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C492123:ZIC1 protein, human; C491812:ZIC2 protein, human; C492122:Zic1 protein, mouse; C491811:Zic2 protein, mouse