Schnurri-2 mutant mice are hypersensitive to stress and hyperactive

Abstract

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.