Chrm5-KO Mouse

Chrm5, encoding the M5 muscarinic acetylcholine receptor, is a seven-transmembrane-spanning G-protein-coupled receptor. It belongs to the muscarinic acetylcholine receptor family and is involved in cholinergic signaling pathways. This signaling is crucial for various physiological functions, such as the regulation of the nervous system, muscle contraction, and glandular secretion [1,2,4].

In a study, a homozygous missense variant (p.Gln184Arg) in Chrm5 was identified in a patient with neurogenic bladder and secondary complications of congenital anomalies of the kidney and urinary tract (CAKUT). Chrm5 is expressed in murine and human bladder walls, and Chrm5 knockout mice show bladder overactivity, suggesting its potential role in neurogenic bladder [1]. In another study, promoter IV-BDNF deficiency in mice led to a significant reduction in Chrm5 mRNA levels in the hippocampus, indicating its role in cholinergic dysfunctions under chronic stress conditions [2]. Also, long-term alcohol consumption in male alcohol-preferring rats up-regulated Chrm5 expression in the ventral subiculum, highlighting its role in alcohol-induced cholinergic dysregulation [3].

In conclusion, Chrm5 is essential for normal cholinergic function and plays important roles in various physiological and pathological processes. Gene knockout mouse models have been valuable in revealing its role in diseases like neurogenic bladder, cholinergic dysfunctions related to stress, and alcohol-related cholinergic dysregulation. Understanding Chrm5's functions can potentially provide insights for the treatment of these associated diseases.

References:

1. Schneider, Sophia, Schierbaum, Luca, Burger, Wessel A C, Thal, David M, Hildebrandt, Friedhelm. 2023. Recessive CHRM5 variant as a potential cause of neurogenic bladder. In American journal of medical genetics. Part A, 191, 2083-2091. doi:10.1002/ajmg.a.63241. https://pubmed.ncbi.nlm.nih.gov/37213061/

2. Sakata, Kazuko, Overacre, Abigail E. 2017. Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: effects of drug and environmental treatments. In Journal of neurochemistry, 143, 49-64. doi:10.1111/jnc.14129. https://pubmed.ncbi.nlm.nih.gov/28722769/

3. Walker, Leigh C, Huckstep, Kate L, Chen, Nicola A, Langmead, Christopher J, Lawrence, Andrew J. 2021. Muscarinic M4 and M5 receptors in the ventral subiculum differentially modulate alcohol seeking versus consumption in male alcohol-preferring rats. In British journal of pharmacology, 178, 3730-3746. doi:10.1111/bph.15513. https://pubmed.ncbi.nlm.nih.gov/33942300/

4. Pedersen, Julia E, Bergqvist, Christina A, Larhammar, Dan. 2018. Evolution of the Muscarinic Acetylcholine Receptors in Vertebrates. In eNeuro, 5, . doi:10.1523/ENEURO.0340-18.2018. https://pubmed.ncbi.nlm.nih.gov/30564629/