Ggt7-KO Mouse

Ggt7, also known as GGTL3 or GGT4, is a member of the gamma-glutamyltransferase gene family. It is involved in multiple biological processes, potentially regulating glutathione metabolism, as gamma-glutamyltransferases are known to have a role in glutathione metabolism [5]. It may also be related to redox-sensitive functions and could play a part in various signaling pathways, given its associations with different diseases. Animal models, such as gene-knockout mouse models, could potentially provide further insights into its in-vivo functions.

In pancreatic cancer, TXNDC12 inhibits ferroptosis in pancreatic cancer cells through the GSH/GGT7 axis, promoting cancer cell growth and metastasis. Knockdown of TXNDC12 decreased intracellular GSH content and increased pro-ferroptosis factors, and these effects could be reversed by overexpression of GGT7 [1].

In gastric cancer, GGT7 is frequently downregulated by promoter methylation. High-expression of GGT7 in adjacent non-tumor tissues is associated with favorable survival. GGT7 significantly inhibits gastric cancer cell growth, cell cycle transition, and migration and invasion abilities, and attenuates xenograft tumor growth and lung metastasis in nude mice. It binds with RAB7 to induce mitophagy, inhibit ROS, and suppress MAPK cascades [2].

In rats with collagen-induced arthritis, downregulation of colonic Ggt7 was observed, and its upregulation by specific bioactive polysaccharides alleviated the arthritis, suggesting its role in this inflammatory condition [3].

In glioblastoma, patients with low GGT7 expression had a worse prognosis. Exogenous expression of GGT7 reduced proliferation and anchorage-independent growth, while decreasing its expression increased proliferation and tumor growth in mice. Enhanced GGT7 expression reduced ROS levels, indicating its role in regulating anti-oxidative damage in glioblastoma [4].

Genetic ablation of Ggt7 in mice led to reduced serum cholesterol levels, suggesting its role in cholesterol homeostasis as a SREBP2-dependent target that positively regulates cellular cholesterol levels [6].

In conclusion, Ggt7 plays diverse and significant roles in multiple biological processes and disease conditions. Its involvement in cancer (pancreatic, gastric, glioblastoma), arthritis, and cholesterol homeostasis has been revealed through various studies, some of which utilized in-vivo models like mouse models. Understanding Ggt7's functions provides potential targets for therapeutic intervention in these diseases.

References:

1. Xu, Xiangrong, Hei, Yu, Wang, Bobo, Zhang, Jing, Wang, Fenghui. 2024. TXNDC12 inhibits pancreatic tumor cells ferroptosis by regulating GSH/GGT7 and promotes its growth and metastasis. In Journal of Cancer, 15, 3913-3929. doi:10.7150/jca.93208. https://pubmed.ncbi.nlm.nih.gov/38911386/

2. Wang, Xiaohong, Zhang, Lianhai, Chan, Francis K L, Yu, Jun, Liang, Jessie Qiaoyi. 2022. Gamma-glutamyltransferase 7 suppresses gastric cancer by cooperating with RAB7 to induce mitophagy. In Oncogene, 41, 3485-3497. doi:10.1038/s41388-022-02339-1. https://pubmed.ncbi.nlm.nih.gov/35662282/

3. Wang, Chunyan, Chen, Yunjing, Zhang, Guangwen, Peng, Xichun, Luo, Jianming. 2020. Recovery of Ggt7 and Ace Expressions in the Colon Alleviates Collagen-Induced Arthritis in Rats by Specific Bioactive Polysaccharide Intervention. In Journal of agricultural and food chemistry, 68, 14531-14539. doi:10.1021/acs.jafc.0c06252. https://pubmed.ncbi.nlm.nih.gov/33226212/

4. Bui, Timothy T, Nitta, Ryan T, Kahn, Suzana A, Recht, Lawrence, Li, Gordon. 2015. γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth. In BMC cancer, 15, 225. doi:10.1186/s12885-015-1232-y. https://pubmed.ncbi.nlm.nih.gov/25884624/

5. Heisterkamp, Nora, Groffen, John, Warburton, David, Sneddon, Tam P. 2008. The human gamma-glutamyltransferase gene family. In Human genetics, 123, 321-32. doi:10.1007/s00439-008-0487-7. https://pubmed.ncbi.nlm.nih.gov/18357469/

6. Shan, Haihuan, Fan, Shuangshuang, Li, Quanrun, Yu, Kun, Fei, Teng. 2025. Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis. In Genome biology, 26, 59. doi:10.1186/s13059-025-03531-8. https://pubmed.ncbi.nlm.nih.gov/40098013/