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 (Zic2 kd/kd). Since human ZIC2 haploinsufficiency is a cause of holoprosencephaly, the Zic2 kd/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 Zic2 kd/+), and significant abnormalities were found in the hanging, spontaneous locomotor activity, stationary rod (Zic1 −/+), acoustic startle response, and prepulse inhibition tests (Zic2 kd/+). 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 Zic2 kd/+ mice may be attributable to the presumed abnormality in the dorsomedial forebrain, which was strongly affected in the Zic2 kd/kd mice. Zic2 kd/+ mice can serve as a model for diseases involving sensorimotor gating abnormalities, such as schizophrenia.
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Ogura, H., Aruga, J. & Mikoshiba, K. Behavioral Abnormalities of Zic1 and Zic2 Mutant Mice: Implications as Models for Human Neurological Disorders. Behav Genet 31, 317–324 (2001). https://doi.org/10.1023/A:1012235510600
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DOI: https://doi.org/10.1023/A:1012235510600