Chrnb4-KO Mouse

Chrnb4, encoding the neuronal acetylcholine receptor subunit beta-4, is part of the nicotinic acetylcholine receptor (nAChR) family. nAChRs are ligand-gated ion channels involved in the central nervous system function, and Chrnb4-containing nAChRs may contribute to nicotine-related behaviors. Genetic variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster is linked to increased vulnerability to tobacco dependence and smoking-associated diseases [1].

In a Chrnb4-cre; Dicerflox/flox conditional knockout (CKO) mouse model, deleting Dicer1 from cone cells using Chrnb4-Cre led to cone photoreceptor cell degeneration and death, along with impaired photopic vision. RNAseq analysis of the Dicer CKO retina revealed altered expression of genes in the visual perception pathway, suggesting Dicer1 is essential for cone photoreceptor survival and homeostasis [3]. Also, Chrnb4 knockdown in esophageal squamous cell carcinoma (ESCC) cells inhibited cell proliferation via the Akt/mTOR and ERK1/2/mTOR pathways, indicating its potential as a biomarker and therapeutic target for ESCC [2].

In summary, Chrnb4 plays a role in nicotine-related behaviors and diseases, and its function in cone photoreceptor survival has been revealed through CKO mouse models. These findings contribute to understanding the mechanisms of tobacco-related diseases and cone-mediated vision loss, highlighting the importance of Chrnb4 in both neural and retinal biological processes.

References:

1. Picciotto, Marina R, Kenny, Paul J. 2021. Mechanisms of Nicotine Addiction. In Cold Spring Harbor perspectives in medicine, 11, . doi:10.1101/cshperspect.a039610. https://pubmed.ncbi.nlm.nih.gov/32341069/

2. Li, Nan, Liu, Kaisheng, Dong, Shaowei, Wang, Xiao, Wang, Shaoxiang. 2020. Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma. In Frontiers in oncology, 10, 571167. doi:10.3389/fonc.2020.571167. https://pubmed.ncbi.nlm.nih.gov/33304845/

3. Aldunate, Eduardo Zabala, Di Foggia, Valentina, Di Marco, Fabiana, Ali, Robin R, Sowden, Jane C. 2019. Conditional Dicer1 depletion using Chrnb4-Cre leads to cone cell death and impaired photopic vision. In Scientific reports, 9, 2314. doi:10.1038/s41598-018-38294-9. https://pubmed.ncbi.nlm.nih.gov/30783126/