Enhanced calcium transients in glial cells in neonatal cerebellar culturesderived from S100B null mice

S100B is the major low-affinity Ca2+-binding protein in astrocytes. In orde r to study the role of S100B in the maintenance of Ca2+ homeostasis, we gen erated S100B null mice by a targeted inactivation of the S100B gene. Absenc e of S100B expression was demonstrated by Northern and Western blotting for S100B mRNA and protein, respectively, and immunoperoxidase staining of sec tions of various brain regions. S100B null mice were viable, fertile, and e xhibited no overt behavioral abnormalities up to 12 months of age. On the b asis of light microscopy and immunohistochemical staining, there were no di scernable alterations in the distribution and morphology of astrocytes or n eurons in sections of adult brains of these mice. Astrocytes in cerebellar cultures derived from 6-day-old S100B null mice exhibited enhanced Ca2+ tra nsients in response to treatment with KCl or caffeine. On the other hand, g ranule neurons, in the same cultures, exhibited normal Ca2+ transients in r esponse to treatment with KCl, caffeine, or N-methyl-D-aspartate. These res ults demonstrate a specific decrease in Ca2+-handling capacity in astrocyte s derived from S100B null mice and suggest that S100B plays a role in the m aintenance of Ca2+ homeostasis in astrocytes. (C) 2000 Academic Press.