Tac4, also associated with encoding hemokinin-1 (HK-1) in mammals, is a gene with diverse functions. It belongs to the tachykinin family and is involved in multiple physiological functions, including pain modulation, stress response, and immune regulation, often acting through the tachykinin NK1 receptor [1,3,5]. Gene-knockout mouse models have been crucial in understanding its role in these processes.

In Tac4-/-mice, stress-induced mechanical hyperalgesia is decreased, indicating HK-1's role in stress-induced pain [1]. These mice also show changes in B lymphocyte development, with an increase in "fraction B" pro-B cells in the bone marrow, suggesting an inhibitory role of HK-1 on developing B cells [4]. Moreover, Tac4-/-mice display altered anxiety and depression-like behaviors, with less time in the lit compartment in the light-dark box, reduced time in the open arms of the elevated plus maze, and increased immobility in the tail suspension and forced swim tests, demonstrating an anxiolytic and anti-depressant-like action of HK-1 [6]. In addition, functional studies of the TAC4 locus in mice revealed that Tac4-/-mice have reduced mechanical bone strength, highlighting its role in bone quality [2].

In conclusion, Tac4 plays essential roles in pain, stress response, immune regulation, and bone quality as revealed through gene-knockout mouse models. These findings contribute to understanding the mechanisms underlying stress-induced pain, hematopoiesis, and bone-related diseases, potentially opening new perspectives for therapeutic development in these areas.

References:

1. Borbély, Éva, Kecskés, Angéla, Kun, József, Palkovits, Miklós, Helyes, Zsuzsanna. 2023. Hemokinin-1 is a mediator of chronic restraint stress-induced pain. In Scientific reports, 13, 20030. doi:10.1038/s41598-023-46402-7. https://pubmed.ncbi.nlm.nih.gov/37973885/

2. Nethander, Maria, Movérare-Skrtic, Sofia, Kämpe, Anders, Richards, J Brent, Ohlsson, Claes. 2023. An atlas of genetic determinants of forearm fracture. In Nature genetics, 55, 1820-1830. doi:10.1038/s41588-023-01527-3. https://pubmed.ncbi.nlm.nih.gov/37919453/

3. Page, N M. . Hemokinins and endokinins. In Cellular and molecular life sciences : CMLS, 61, 1652-63. doi:. https://pubmed.ncbi.nlm.nih.gov/15224188/

4. Berger, Alexandra, Benveniste, Patricia, Corfe, Steven A, Iscove, Norman N, Paige, Christopher J. 2010. Targeted deletion of the tachykinin 4 gene (TAC4-/-) influences the early stages of B lymphocyte development. In Blood, 116, 3792-801. doi:10.1182/blood-2010-06-291062. https://pubmed.ncbi.nlm.nih.gov/20660792/

5. Borbély, Éva, Helyes, Zsuzsanna. 2016. Role of hemokinin-1 in health and disease. In Neuropeptides, 64, 9-17. doi:10.1016/j.npep.2016.12.003. https://pubmed.ncbi.nlm.nih.gov/27993375/

6. Borbély, Éva, Hajna, Zsófia, Nabi, Liza, Berger, Alexandra, Helyes, Zsuzsanna. 2016. Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice. In Brain, behavior, and immunity, 59, 219-232. doi:10.1016/j.bbi.2016.09.004. https://pubmed.ncbi.nlm.nih.gov/27621226/