title: Smad2 protein disruption in the central nervous system leads to aberrant cerebellar development and early postnatal ataxia in mice.
abstract: Smad2 is a critical mediator of TGF-β signals that are known to play an important role in a wide range of biological processes in various cell types. Its role in the development of the CNS, however, is largely unknown. Mice lacking Smad2 in the CNS (Smad2-CNS-KO) were generated by a Cre-loxP approach. These mice exhibited behavioral abnormalities in motor coordination from an early postnatal stage and mortality at approximately 3 weeks of age, suggestive of severe cerebellar dysfunction. Gross observation of Smad2-CNS-KO cerebella demonstrated aberrant foliations in lobule IX and X. Further analyses revealed increased apoptotic cell death, delayed migration and maturation of granule cells, and retardation of dendritic arborization of Purkinje cells. These findings indicate that Smad2 plays a key role in cerebellar development and motor function control.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Goto
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Tanaka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Abe
authors.forename: Shohei
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.forename: Patricio L M
authors.initials: PL
authors.lastname: Enciso
authors.forename: Masahiro
authors.initials: M
authors.lastname: Adachi
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Hisaya
authors.initials: H
authors.lastname: Kawate
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D002465:Cell Movement; D002524:Cerebellar Ataxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051899:Smad2 Protein; C497783:Smad2 protein, mouse