Tbc1d8-KO Mouse

Tbc1d8, a member of the TBC domain protein family, is involved in various biological processes. While its exact core function in normal biological pathways isn't comprehensively defined from these abstracts, its role in disease-related processes has been explored. Genetic models could potentially be valuable in further elucidating its normal function and associated pathways [1,3].

In cancer research, Tbc1d8 is significantly up-regulated in aggressive ovarian cancer cells, and its amplification promotes ovarian cancer tumorigenesis and metabolic reprogramming by binding to PKM2, hindering its tetramerization, and promoting its nuclear translocation [1]. In colorectal cancer, it may act as an oncogene and is associated with hypoxia and M2 macrophage infiltration [3]. In osteoporosis research, reduced CpG island methylation of the Tbc1D8 gene in Chinese postmenopausal women is associated with osteoporosis, and it shows a negative correlation with high-density lipoprotein in these patients [2].

In conclusion, Tbc1d8 appears to play crucial roles in cancer development, specifically in ovarian and colorectal cancer, and is also associated with osteoporosis. Functional studies, potentially through gene knockout or conditional knockout mouse models in the future, could further clarify its role in these disease conditions, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Chen, Min, Sheng, Xiu-Jie, Qin, Yuan-Yi, He, Yu-Tian, Yan, Guang-Rong. 2019. TBC1D8 Amplification Drives Tumorigenesis through Metabolism Reprogramming in Ovarian Cancer. In Theranostics, 9, 676-690. doi:10.7150/thno.30224. https://pubmed.ncbi.nlm.nih.gov/30809301/

2. Ma, Qian-Qian, Lin, Lv, Yao, Qi, Hu, Yan, Yu, Jing-Bo. 2018. Reduced CpG island methylation of the TBC1D8 gene may predict risk for osteoporosis in Chinese postmenopausal women. In Oncotarget, 11, 4448-4456. doi:10.18632/oncotarget.24065. https://pubmed.ncbi.nlm.nih.gov/33315972/

3. Liu, Yuan-Jie, Li, Jie-Pin, Li, Hui-Ru, Liu, Shen-Lin, Zou, Xi. 2022. An analysis of the significance of the Tre2/Bub2/CDC 16 (TBC) domain protein family 8 in colorectal cancer. In Scientific reports, 12, 13245. doi:10.1038/s41598-022-15629-1. https://pubmed.ncbi.nlm.nih.gov/35918393/