EXPRESSION OF THE RAT CALMODULIN GENE-II IN THE CENTRAL-NERVOUS-SYSTEM - A 294-BASE PROMOTER AND 68-BASE LEADER SEGMENT MEDIATES NEURON-SPECIFIC GENE-EXPRESSION IN TRANSGENIC MICE

Deletion analysis of the rat CaMII promoter demonstrated that the segment from - 294 to + 68 bases of CaMII was efficient as a promoter in NIH3T3 by transient assay. We developed transgenic mice carrying a fusion gene of this promoter segment and a beta-galactosidase reporter gene. This short CaMII promoter mediated the transgene expression in pyramidal cells of the cerebral neocortex, the pyriformcortex and the hippocampal regions CA1 to CA3, in granule cells of the dentate gyrus, in Purkinje cells of the cerebellum, and in neurons of the lateral vestibular nucleus of pons and the spinal cord of adult transgenic mice. The expression of endogenous CaMII was precisely analyzed by in situ hybridization in the nervous tissues. The localization of transgene expression was consistent with those of the endogenous CaMII in the adult transgenic mice. In the embryos at 13.5-15.5 days of gestation, the transgene was expressed in various neurons similarly to the endogenous CaMII but certain subtle differences were observed in the localization of expression. This short promoter of rat CaMII carried two sequence stretches highly conserved in the mouse, dog, chicken and Xenopus CaMII promoters. These conserved stretches may be involved in the observed neuron-specific expression of rat CaMII gene.