Chrna6, which encodes the α6 subunit of nicotinic acetylcholine receptors (nAChR), is part of ligand-gated ion channels. These receptors are involved in the cholinergic modulation of dopamine release in the striatum, and the CHRNB3-Chrna6 gene cluster on chromosome 8 has been implicated in nicotine dependence [1]. It also participates in other biological processes, potentially related to immune responses and neurodegenerative-like phenotypes.

In nicotine-related research, genetic manipulation in mice has shown that α6 *-nAChRs in the ventral tegmental area (VTA) are crucial in controlling nicotine self-administration. When the α6 subunit is selectively re-expressed in the VTA of the α6(-/-) mouse by a lentiviral vector, the reinforcing property of nicotine is restored [1]. In a study of a child with severe infantile parkinsonism, a de novo missense mutation in Chrna6 was found, and in silico, in vitro (Xenopus oocytes and GH4C1 cells) and in vivo (C. elegans) analyses demonstrated the disruptive effects of the mutation on acetylcholine receptor structure and function, suggesting Chrna6 as a genetic modifier of the phenotype [2].

In conclusion, Chrna6 is essential for the function of nAChRs, playing a role in processes such as nicotine dependence and potentially as a genetic modifier in neurodegenerative-like conditions. Studies using gene-manipulated mouse models and other in vivo models have provided key insights into its function in these specific disease-related areas.

References:

1. Wen, L, Yang, Z, Cui, W, Li, M D. 2016. Crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research. In Translational psychiatry, 6, e843. doi:10.1038/tp.2016.103. https://pubmed.ncbi.nlm.nih.gov/27327258/

2. Martinelli, Simone, Cordeddu, Viviana, Galosi, Serena, Tartaglia, Marco, Leuzzi, Vincenzo. 2020. Co-occurring WARS2 and CHRNA6 mutations in a child with a severe form of infantile parkinsonism. In Parkinsonism & related disorders, 72, 75-79. doi:10.1016/j.parkreldis.2020.02.003. https://pubmed.ncbi.nlm.nih.gov/32120303/