Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Behavioral abnormalities of Zic1 and Zic2 mutant mice: implications as models for human neurological disorders. 1169 4

Zic family proteins have been investigated in various biomedical studies. Here we summarize the contact points between Zic proteins and recent medical research. The topics cover a wide range, reflecting the pleiotropic roles of these proteins in early embryogenesis and organogenesis. Zic1, Zic2, and Zic3 proteins play important roles in the development of axial and limb bones, and of muscles, among the derivatives of the notochord and somites. Zic1 is involved in bone's response to mechanical stress, and it also serves as a marker specific for brown adipocytes. Zic1, Zic2, Zic3, and Zic5 proteins are required for the development of neural crest derivatives, including the meningeal membrane and facial bones, and deficiency of these proteins causes cortical lamination defects resembling those in type II lissencephaly. In vascular systems, Zic3 is associated not only with normal cardiovascular development, failure of which causes congenital heart anomalies, but also controls maturation of the blood-brain barrier. Zic1 is also expressed in the brain pericytes possessing stem cell properties that control the blood-brain barrier activity and capillary hemodynamic responses. The possible involvement of Zic proteins in neuropsychiatric disorders has been indicated by the analyses of mutant mice behaviors. Zic1 and Zic3 mutant mice show hypotonia and decreased locomotor activities. Zic2 hypomorphic mutant mice exhibit schizophrenia-related behavioral abnormalities such as cognitive dysfunction and impaired sensorimotor gating and social behaviors, and ZIC2 mutations found in schizophrenia patients included a severely functionally defective one. Based on these facts, the application of Zic protein activities in translational medicine might be considered.
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PMID:Zic Family Proteins in Emerging Biomedical Studies. 2944 25