The 5 '-flanking region of the mouse adenylyl cyclase type VIII gene imparts tissue-specific expression in transgenic mice

The calcium-stimulated adenylyl cyclases (ACs) play a central role in stimu lus-dependent modification of synaptic function. The type VIII AC (AC8) is one of three mammalian calcium-stimulated isoforms, each of which is expres sed in a region-specific manner in the CNS. To delineate the DNA sequences responsible for appropriate targeting of AC8 expression, we report here the complete structure of the AC8 gene and define the pattern of expression of the full-length cDNA and its splice variants. In addition to expression wi thin the brain, robust expression of AC8 was also found in the lung. By in situ hybridization, we have found the highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula, cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei. By generating transgenic mice whose expression of beta-galactosidase is controlled by the AC8 5'-flanking DNA s equences, we demonstrate that the DNA sequences within the 10 kb preceding exon 1 are critical for establishment of this region-specific pattern. This spectrum of sites of production is unique to AC8 among the calcium-stimula ted adenylyl cyclases and suggests nonredundant functions with other adenyl yl cyclases in neuroendocrine regulation and/or behavior.