Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressedin the primitive ventricle of the heart and during neurogenesis

We have demonstrated that DSCR1 acts as a negative regulator of calcineurin -mediated signaling and that its transcript is overexpressed in the Down sy ndrome (DS) fetal brain. To evaluate the possible involvement of DSCR1 in D S, we have cloned the mouse gene and analyzed its expression pattern in the central nervous system (CNS). Early expression of Dscr1 is detected mainly in the heart tube and in the CNS in rhombomere 4 and the pretectum. From e mbryonic day 14.5 onwards. Dscr1 is widely distributed in the CNS but becom es more restricted as the brain matures. We confirmed its neuronal expressi on pattern in the adult, preferentially in Purkinje and pyramidal cells, by double labeling with glial fibrillary acidic protein. We also show that al though Dscr1 is present in trisomy in the Ts65Dn mouse, the adult brain exp ression pattern is not significantly altered. Thin expression pattern indic ated that Dscr1 is a developmentally regulated gene involved in neurogenesi s and cardiogenesis and suggests that it may contribute to the alterations observed in these organ systems in DS patients. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.