Tmem79-KO Mouse

Tmem79, also known as MATTRIN, is an orphan multi-span transmembrane protein. It has diverse essential functions, being involved in regulating multiple biological pathways. It is a key regulator in Wnt/FZD signaling, and is also associated with thermosensation, inflammation, oxidative stress, and skin barrier function. Genetic models, especially KO/CKO mouse models, have been crucial for studying its functions [2,3,5,6,7].

In KO mouse models, Tmem79-deficient male mice preferred a higher temperature due to elevated TRPV3 function, indicating its role as a negative regulator of TRPV3 in thermosensation [1]. Tmem79-deficient mice also developed spontaneous dermatitis, with the first-phase being microbiota-independent and associated with increased sebaceous lipid production. They also showed IL-17A-dependent spontaneous AD-like inflammation, and had a defective skin barrier leading to secondary lung inflammation [5,6]. Moreover, Tmem79-deficient mice had pre-existing inflammation that reduced the response to contact allergens [4]. In the context of cerebral ischemia/reperfusion injury, overexpression of Tmem79 in a mouse model mitigated the injury by regulating the Nrf2/NLRP3 pathway [3].

In conclusion, Tmem79 plays essential roles in thermosensation, skin barrier maintenance, and the regulation of inflammation and oxidative stress. The use of Tmem79 KO mouse models has provided valuable insights into its functions, especially in relation to atopic dermatitis, cerebral ischemia/reperfusion injury, and thermosensation-related diseases.

References:

1. Lei, Jing, Yoshimoto, Reiko U, Matsui, Takeshi, Kido, Mizuho A, Tominaga, Makoto. 2023. Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice. In Nature communications, 14, 4104. doi:10.1038/s41467-023-39712-x. https://pubmed.ncbi.nlm.nih.gov/37474531/

2. Chen, Maorong, Amado, Nathalia, Tan, Jieqiong, Abreu, Jose Garcia, He, Xi. 2020. TMEM79/MATTRIN defines a pathway for Frizzled regulation and is required for Xenopus embryogenesis. In eLife, 9, . doi:10.7554/eLife.56793. https://pubmed.ncbi.nlm.nih.gov/32924931/

3. Zhang, Wei, Fan, Chengcheng, Yi, Zhongxue, Ma, Xiande, Wang, Zhe. 2024. TMEM79 Ameliorates Cerebral Ischemia/Reperfusion Injury Through Regulating Inflammation and Oxidative Stress via the Nrf2/NLRP3 Pathway. In Immunological investigations, 53, 872-890. doi:10.1080/08820139.2024.2354268. https://pubmed.ncbi.nlm.nih.gov/38809063/

4. Jee, Mia Hamilton, Funch, Anders Boutrup, Weber, Julie Friis, Geisler, Carsten, Bonefeld, Charlotte Menné. 2024. Pre-existing inflammation reduces the response to contact allergens in Tmem79-deficient mice. In Allergy, 79, 1978-1981. doi:10.1111/all.16053. https://pubmed.ncbi.nlm.nih.gov/38366993/

5. Saunders, Sean P, Floudas, Achilleas, Moran, Tara, Fallon, Padraic G, Schwartz, Christian. 2020. Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation. In Allergy, 75, 3216-3227. doi:10.1111/all.14488. https://pubmed.ncbi.nlm.nih.gov/32644214/

6. Morimoto, Ari, Fukuda, Keitaro, Ito, Yoshihiro, Matsui, Takeshi, Amagai, Masayuki. 2022. Microbiota-Independent Spontaneous Dermatitis Associated with Increased Sebaceous Lipid Production in Tmem79-Deficient Mice. In The Journal of investigative dermatology, 142, 2864-2872.e6. doi:10.1016/j.jid.2022.06.003. https://pubmed.ncbi.nlm.nih.gov/35752300/

7. Emrick, Joshua J, Mathur, Anubhav, Wei, Jessica, Rosenblum, Michael D, Julius, David. 2018. Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch. In Proceedings of the National Academy of Sciences of the United States of America, 115, E12091-E12100. doi:10.1073/pnas.1814132115. https://pubmed.ncbi.nlm.nih.gov/30463955/