CHRNA7, encoding the α7 neuronal nicotinic acetylcholine receptor, is ubiquitously expressed in the central nervous system and periphery. It is involved in cholinergic neurotransmission, and its function is crucial for normal cognitive processes. The regulation of CHRNA7 is complex, with a partial duplication creating the CHRFAM7A gene that can dominantly negatively regulate CHRNA7 function [1].

Chrna7 deficient mice have been studied to understand its role in diseases. However, these mice did not show consistent neuropsychiatric and behavioral phenotypes related to human conditions like schizophrenia, bipolar disorder, epilepsy, etc. [4]. In contrast, CHRNA7 copy number variants in humans are associated with multiple neuropsychiatric conditions. Deletions are linked to more severe phenotypes, such as in Rett syndrome, and are enriched in risperidone-treated children and adolescents with severe aggression [3,5]. Gains are relatively prevalent among adolescents with major depressive and anxiety disorders [6]. Also, mutations in RIC3, a chaperone of CHRNA7, provide evidence for the role of the cholinergic pathway in Parkinson's disease [2].

In summary, CHRNA7 is vital for cholinergic neurotransmission and normal cognitive function. While Chrna7 knockout mouse models have not fully replicated human disease phenotypes, studies on human CHRNA7 copy number variants and associated chaperone mutations have revealed its significant role in various neuropsychiatric and neurodegenerative diseases.

References:

1. Sinkus, Melissa L, Graw, Sharon, Freedman, Robert, Lester, Henry A, Leonard, Sherry. 2015. The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function. In Neuropharmacology, 96, 274-88. doi:10.1016/j.neuropharm.2015.02.006. https://pubmed.ncbi.nlm.nih.gov/25701707/

2. Cherian, Ajith, K P, Divya, Vijayaraghavan, Asish. 2023. Parkinson's disease - genetic cause. In Current opinion in neurology, 36, 292-301. doi:10.1097/WCO.0000000000001167. https://pubmed.ncbi.nlm.nih.gov/37366140/

3. Gillentine, Madelyn A, Schaaf, Christian P. 2015. The human clinical phenotypes of altered CHRNA7 copy number. In Biochemical pharmacology, 97, 352-362. doi:10.1016/j.bcp.2015.06.012. https://pubmed.ncbi.nlm.nih.gov/26095975/

4. Yin, Jiani, Chen, Wu, Yang, Hongxing, Xue, Mingshan, Schaaf, Christian P. 2017. Chrna7 deficient mice manifest no consistent neuropsychiatric and behavioral phenotypes. In Scientific reports, 7, 39941. doi:10.1038/srep39941. https://pubmed.ncbi.nlm.nih.gov/28045139/

5. Gillentine, Madelyn A, White, Janson J, Grochowski, Christopher M, Schaaf, Christian P, Calarge, Chadi A. 2017. CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents. In Journal of child and adolescent psychopharmacology, 27, 908-915. doi:10.1089/cap.2017.0068. https://pubmed.ncbi.nlm.nih.gov/28817303/

6. Gillentine, Madelyn A, Lozoya, Ricardo, Yin, Jiani, Schaaf, Christian P, Calarge, Chadi A. 2018. CHRNA7 copy number gains are enriched in adolescents with major depressive and anxiety disorders. In Journal of affective disorders, 239, 247-252. doi:10.1016/j.jad.2018.07.017. https://pubmed.ncbi.nlm.nih.gov/30029151/