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

Abstract

Rat connexin-36 (Cx36) is the first gap junction protein shown to be expressed predominantly in neuronal cells of the mammalian central nervous system. As a prerequisite for studies devoted to the investigation of the possible role of this connexin in human neurological diseases, we report the cloning and sequencing of the human Cx36 gene, its chromosomal localization, and its pattern of expression in the human brain analyzed by radioactive in situ hybridization. The determination of the human gene sequence revealed that the coding sequence of Cx36 is highly conserved (98% identity at the protein level with the mouse and rat Cx36 and 80% with the ortholog perch and skate Cx35), and that the gene structure is that typical of the Cx35/36 subgroup observed in the other species (presence of a single intron located within the coding region, 71 bp after the translation initiation site). The distribution of Cx36 in several regions of the human central nervous system is 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 moderate labeling was also observed in several myelencephalic nuclei, in specific cells of the the cerebellar cortex, in a relatively large subpopulation of cells in the cerebral cortex, in the hilus of the dentate gyrus, and in the strata radiatum and oriens of hippocampal subfields. Moreover, labeled cells were revealed in all the lamina of the spinal cord gray matter. The chromosomal localization of the human Cx36 gene was determined by fluorescence in situ hybridization. The results allowed assignment of the gene to band 15q14, thus making it a possible candidate gene for a form of familial epilepsy previously linked to the same chromosomal band. The knowledge of the human Cx36 gene sequence, of its chromosomal localization, and of its pattern of expression opens new avenues for the analysis of its possible involvement in human genetic and acquired neuropathology.

Developmental regulation of connexins 26, 32, 36, and 43 in trigeminal neurons

“…Cx36 is of interest because its expression is restricted to neurons , and forms only homotypic channels (Al-Ubaidi et al, 2000). Our findings of a decrease in Cx36 expression in trigeminal motoneurons are similar to those of Belluardo et al (2000) showing a decrease in Cx36 mRNA expression in rat spinal motoneurons, but differ from in situ hybridization studies showing a moderate to high density of Cx36 mRNA expression in adult human spinal motoneurons and hypoglossal motoneurons (Belluardo et al, 1999) and rat spinal motoneurons (Chang et al, 1999). Our data regarding the developmental expression of Cx43 in trigeminal motoneurons is similar to that described by Chang et al (1999) for rat spinal motoneurons, but our data for Cx26 and Cx32 expression differs from the results of Chang et al (1999) who reported that Cx32 and Cx26 mRNA were not expressed in spinal motoneurons at any age.…”

Functional Expression of the Murine Connexin 36 Gene Coding for a Neuron-Specific Gap Junctional Protein

“…This region corresponds to the human chromosome 15. Very recently, Belluardo et al (1999) reported that the human Cx36 gene is located on the human chromosome 15q14, to which a juvenile form of myoclonic epilepsy has been mapped. It will be of interest to establish whether mutation(s) in the Cx36 gene cause this form of epilepsy.…”

Genetics as a tool for the dissociation of mental operations over the course of development

“…CX36 is expressed throughout the CNS: in the retina, inferior olivary complex, cerebellum, hippocampus, thalamus, striatum, and in the neocortex, particularly in layers IV and VI. [90][91][92][93][94][95] CX36 within the CNS is primarily neuronal 92,96 and appears to be most prevalent in interneruons, 97 although it has also been identified in mouse and human microglia. 98 Coupling between internurons of individual classes 75,99 allows for the control of neuronal oscillations across a wide range of frequencies, and CX36 appears to be important for this.…”