Schnurri-2 mutant mice are hypersensitive to stress and hyperactive.
The bone morphogenetic protein (BMP)/transforming growth factor-beta (TGF-beta)/activin superfamily regulates development of the nervous system during embryogenesis and is also suggested to be involved in adult brain function. However, how BMP/TGF-beta/activin signals modulate neuronal function remains unknown. Schnurri is a transcription factor that contains two metal finger regions. Mammalian Shn-2 enters the nucleus from the cytoplasm in response to BMP-2 stimulation and plays an important role in BMP-dependent adipogenesis. To investigate whether mammalian Shn plays a role in adult brain function, we examined the behaviors of mutant mice lacking Shn-2 (Shn-2(-/-)). Shn-2(-/-) mice exhibited hypersensitivity to stress accompanied by anxiety-like behavior. Consistent with this, stress-induced corticosterone levels were significantly higher in Shn-2(-/-) mice compared to wild-type controls. Interestingly, Shn-2(-/-) mice were more active than wild-type mice in a familiar environment. The basal and stress-induced expression levels of the immediate early genes, including c-Fos, were decreased in Shn-2(-/-) mice compared to wild-type mice. Thus, Shn-2 plays a critical role in locomotion and anxiety-like behavior.
Takagi
Tsuyoshi
T
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Jin
Wanzhu
W
Taya
Kazuyoshi
K
Watanabe
Gen
G
Mori
Kensaku
K
Ishii
Shunsuke
S
D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D017781:Genes, Immediate-Early / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011595:Psychomotor Agitation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D003345:Corticosterone