Targeted calretinin expression in granule cells of calretinin-null mice restores normal cerebellar functions

SPECIFIC AIMS
Inactivation of gene coding for calretinin, a calcium binding protein acting as a fast calcium buffer, deeply altered the cerebellar physiology leading to motor discoordination. Although mechanistic hypotheses have been proposed to explain these alterations, the widespread expression of calretinin in the whole central nervous system and its expression in several neuronal types in the cerebellar circuitry preclude a precise mechanistic demonstration. The aim of this study was to determine to what extent the expression of calretinin in a specific neuronal cell type, the cerebellar granule cells, contributes to the phenotype detected in calretinin knockout (Cr–/–) mice. To achieve this objective, we constructed transgenic Cr–/– mice exhibiting a selective re-expression of Cr in granule cells (hereafter referred to as Cr-rescue) through the promoter function of the GABAA receptor {alpha}6 subunit gene.