Cerebellar deficits and hyperactivity in mice lacking Smad4.
Smad4 is a central mediator of TGF-beta 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-beta/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.
Zhou
Yong-Xing
YX
Mammalian Genetics Section, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, Bethesda, MD 20892, USA..
Zhao
Mingrui
M
Li
Dan
D
Shimazu
Kazuhiro
K
Sakata
Kazuko
K
Deng
Chu-Xia
CX
Lu
Bai
B
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002531:Cerebellum / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D006948:Hyperkinesis / Q000209:etiology / Q000473:pathology*; D007395:Interneurons / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000473:pathology; D051901:Smad4 Protein; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators