Carnos1, or carnosine synthase 1, is an enzyme that catalyzes the synthesis of carnosine, a histidine-containing dipeptide (HCD) [1,2,3,4,5]. Carnosine has been associated with multiple biological functions such as antioxidant activity, pH regulation, and modulation of Ca2+ handling [2,3,5]. Genetic models, like KO mouse models, have been crucial in studying Carns1's role.

In multiple sclerosis models, Carns1 expression in oligodendrocytes is diminished in demyelinated lesions, and Carns1-KO mice show exaggerated neuroinflammation and worsened clinical symptoms, suggesting its role in endogenous protection against neuroinflammation [2]. In the brain, Carns1-KO old female mice exhibit hyperactivity-and depression-like behaviors, highlighting its link to behavioral regulation [4]. In cardiac muscle, CARNS1-KO rats display impaired contractile function, indicating HCDs synthesized by Carns1 are key regulators of excitation-contraction coupling [5]. Also, exercise-induced protection of hematopoietic stem cells against radiation was abrogated by specific deletion of Carns1 in skeletal muscles, showing its role in this protective mechanism [6].

In conclusion, Carns1 plays essential roles in various biological processes including neuroinflammation regulation, behavior modulation, cardiac muscle function, and exercise-mediated protection of hematopoietic stem cells. The use of KO mouse and rat models has been instrumental in uncovering these functions, providing insights into related disease areas such as multiple sclerosis, behavioral disorders, and radiation-induced hematopoietic injury.

References:

1. Zhang, Li, Zhang, Yan, Zhang, Xin, He, Miao, Qiao, Shixing. 2021. Combining bioinformatics analysis and experiments to explore CARNS1 as a prognostic biomarker for breast cancer. In Molecular genetics & genomic medicine, 9, e1586. doi:10.1002/mgg3.1586. https://pubmed.ncbi.nlm.nih.gov/33533160/

2. Spaas, Jan, Van der Stede, Thibaux, de Jager, Sarah, Eijnde, Bert O, Derave, Wim. 2023. Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis. In Progress in neurobiology, 231, 102532. doi:10.1016/j.pneurobio.2023.102532. https://pubmed.ncbi.nlm.nih.gov/37774767/

3. Sajrawi, Clara, Odeh, Maali, Tiwari, Akshay K, Engelender, Simone, Wolosker, Herman. 2024. Endogenous histidine peptides are physiological antioxidants that prevent oligodendrocyte cell death and myelin loss in vivo. In Glia, 73, 122-139. doi:10.1002/glia.24624. https://pubmed.ncbi.nlm.nih.gov/39360557/

4. Braga, Jason D, Komaru, Takumi, Umino, Mitsuki, Nishimura, Toshihide, Kumrungsee, Thanutchaporn. 2024. Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice. In Biochemical and biophysical research communications, 729, 150361. doi:10.1016/j.bbrc.2024.150361. https://pubmed.ncbi.nlm.nih.gov/38972141/

5. Gonçalves, Lívia de Souza, Sales, Lucas Peixoto, Saito, Tiemi Raquel, Ferreira, Julio Cesar Batista, Artioli, Guilherme Giannini. 2021. Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model. In Redox biology, 44, 102016. doi:10.1016/j.redox.2021.102016. https://pubmed.ncbi.nlm.nih.gov/34038814/

6. Zeng, Hao, Chen, Naicheng, Chen, Fang, Wang, Junping, Hu, Mengjia. 2024. Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis. In Cell communication and signaling : CCS, 22, 582. doi:10.1186/s12964-024-01959-2. https://pubmed.ncbi.nlm.nih.gov/39627813/