Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Smad4 is a central mediator of TGF-β signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-β/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-10, Vol.278 (43), p.42313-42320
Main Authors: Zhou, Yong-Xing, Zhao, Mingrui, Li, Dan, Shimazu, Kazuhiro, Sakata, Kazuko, Deng, Chu-Xia, Lu, Bai
Format: Article
Language:English
Subjects:
Animals
Brain - growth & development
Brain - pathology
Brain - physiopathology
Cell Count
Cerebellar Diseases - genetics
Cerebellar Diseases - pathology
Cerebellar Diseases - physiopathology
Cerebellum - growth & development
Cerebellum - pathology
Cerebellum - physiopathology
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Hippocampus - cytology
Hyperkinesis - etiology
Hyperkinesis - pathology
Interneurons - pathology
Mice
Mice, Knockout
Purkinje Cells - pathology
Smad4 Protein
Trans-Activators - deficiency
Trans-Activators - genetics
Trans-Activators - physiology
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Summary:Smad4 is a central mediator of TGF-β signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-β/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M308287200