Neuron-specific expression of reporter gene in transgenic mice carrying the 5'-upstream region of mouse P/Q-type Ca2+ channel alpha(1A) subunit gene fused to E-coli laZ reporter gene

To dissect the molecular mechanisms underlying the neuron-specific expressi on of the P/Q type calcium channel or,, subunit gene, transgenic mice carry ing a 0.5-kb, 1.5-kb, 3.0-kb or 6.3-kb 5'-upstream region of the gene fused to Escherichia coli lacZ reporter gene were produced. In transgenic mice c arrying the 1.5-kb, 3.0-kb or 6.3-kb 5'-upstream region, the reporter gene was exclusively expressed in the nervous system, although those with the 0. 5-kb 5'-upstream region failed to show reporter expression. Histological ex aminations showed that the three 5'-upstream regions induced distinct expre ssion patterns of the reporter gene in the CNS and adrenal medulla. The 1.5 -kb 5'-upstream region drove reporter gene expression in the olfactory bulb , dorsal cortex and hippocampus, while the regulatory element for the expre ssion in the amygdaloid nucleus, septum, habenula medial nucleus, choroid p lexus, substantia nigra, inferior colliculus, pontine nucleus and cerebellu m was located in the 5'-upstream sequence between 1.5 kb and 6.3 kb. In the cerebellum, the expression of the reporter gene was induced by the 3.0-kb region in granule cells, whereas it was induced by the 6.3-kb region in Pur kinje cells. The expression of the reporter gene in chromaffin cells in the adrenal medulla was induced only by the 6.3-kb 5'-upstream region. These r esults suggest that the expression of the mouse P/Q-type Ca2+ channel alpha (1A) subunit gene is regulated in a complex fashion by both positive and ne gative cis-regulatory elements. (C) 1999 Elsevier Science B.V. All rights r eserved.