Structure, chromosomal localization, and brain expression of human Cx36 gene

Rat connexin-36 (Cx36) is the first gap junction protein shown to be expres sed predominantly in neuronal cells of the mammalian central nervous system . As a prerequisite for studies devoted to the investigation of the possibl e role of this connexin in human neurological diseases, we report the cloni ng and sequencing of the human Cx36 gene, its chromosomal localization, and its pattern of expression in the human brain analyzed by radioactive in si tu hybridization, The determination of the human gene sequence revealed tha t the coding sequence of Cx36 is highly conserved (98% identity at the prot ein level with the mouse and rat Cx36 and 80% with the ortholog perch and s kate Cx35), and that the gene structure is that typical of the Cx35/36 subg roup observed in the other species (presence of a single intron located wit hin the coding region, 71 bp after the translation initiation site). The di stribution of Cx36 in several regions of the human central nervous system i s similar to that previously observed in rat brain. The most intense signal among the cerebral areas examined by in situ hybridization was observed in the inferior olivary complex, both in principal and accessory nuclei. A mo derate labeling was also observed in several myelencephalic nuclei, in spec ific cells of the the cerebellar cortex, in a relatively large subpopulatio n of cells in the cerebral cortex, in the hilus of the dentate gyrus, and i n the strata radiatum and oriens of hippocampal subfields, Moreover, labele d cells were revealed in all the lamina of the spinal cord gray matter. The chromosomal localization of the human Cx36 gene was determined by fluoresc ence in situ hybridization, The results allowed assignment of the gene to b and 15q14, thus making it a possible candidate gene for a form of familial epilepsy previously linked to the same chromosomal band. The knowledge of t he human Cx36 gene sequence, of its chromosomal localization, and of its pa ttern of expression opens new avenues for the analysis of its possible invo lvement in human genetic and acquired neuropathology, (C) 1999 Wiley-Liss, Inc.