Fbxo47-KO Mouse

Fbxo47, an F-box protein, is a key component of the centromeric SCF E3 ubiquitin ligase complex. It is involved in crucial meiotic processes, such as centromere pairing, telomere-inner nuclear envelope integration, and synaptonemal complex stability [1,2,3]. These functions are vital for proper homologous chromosome synapsis, recombination, and successful spermatogenesis. Mouse models have been instrumental in understanding its functions.

In mouse models, knockout of Fbxo47 leads to male infertility. Fbxo47-deficient spermatocytes show defective centromere pairing, incomplete synaptonemal complex formation, and premature dissociation of chromosomes [1,2,3]. FBXO47 interacts with proteins like SKP1 and TRF1/2, stabilizing them. For instance, it down-regulates SKP1 ubiquitination in HEK293T cells and disruption of Fbxo47 destabilizes TRF2 [1,2]. In fish, Foxl3, a gene related to testis development, can upregulate Fbxo47, suggesting its role in gonadal development [4,6]. In addition, in gastric cancer and non-small cell lung cancer, tRF-3019a and GABPB1-AS1 respectively regulate FBXO47, affecting cancer cell proliferation, migration, and invasion [5,7].

In summary, Fbxo47 plays essential roles in meiotic processes, especially in spermatogenesis and chromosome synapsis. Mouse knockout models have been crucial in revealing these functions. Its dysregulation is associated with male infertility and cancer-related phenotypes, highlighting its importance in both reproductive and cancer research [1-3,6,10].

References:

1. Ma, Ani, Yang, Yali, Cao, Lianbao, Chen, Lijun, Zhang, Jian V. 2024. FBXO47 regulates centromere pairing as key component of centromeric SCF E3 ligase in mouse spermatocytes. In Communications biology, 7, 1099. doi:10.1038/s42003-024-06782-6. https://pubmed.ncbi.nlm.nih.gov/39244596/

2. Hua, Rong, Wei, Huafang, Liu, Chao, Li, Wei, Liu, Mingxi. . FBXO47 regulates telomere-inner nuclear envelope integration by stabilizing TRF2 during meiosis. In Nucleic acids research, 47, 11755-11770. doi:10.1093/nar/gkz992. https://pubmed.ncbi.nlm.nih.gov/31724724/

3. Tanno, Nobuhiro, Takemoto, Kazumasa, Takada-Horisawa, Yuki, Araki, Kimi, Ishiguro, Kei-Ichiro. 2022. FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis. In iScience, 25, 104008. doi:10.1016/j.isci.2022.104008. https://pubmed.ncbi.nlm.nih.gov/35310947/

4. Lin, Fangmei, Tong, Feng, He, Qi, Wang, Qing, Zhao, Huihong. 2020. In vitro effects of androgen on testicular development by the AR-foxl3-rec8/fbxo47 axis in orange-spotted grouper (Epinephelus coioides). In General and comparative endocrinology, 292, 113435. doi:10.1016/j.ygcen.2020.113435. https://pubmed.ncbi.nlm.nih.gov/32057909/

5. Zhang, Fei, Shi, Jinxin, Wu, Zhonghua, Song, Yongxi, Wang, Zhenning. 2020. A 3'-tRNA-derived fragment enhances cell proliferation, migration and invasion in gastric cancer by targeting FBXO47. In Archives of biochemistry and biophysics, 690, 108467. doi:10.1016/j.abb.2020.108467. https://pubmed.ncbi.nlm.nih.gov/32592804/

6. Kikuchi, Mariko, Nishimura, Toshiya, Ishishita, Satoshi, Matsuda, Yoichi, Tanaka, Minoru. 2020. foxl3, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka. In Proceedings of the National Academy of Sciences of the United States of America, 117, 12174-12181. doi:10.1073/pnas.1918556117. https://pubmed.ncbi.nlm.nih.gov/32409601/

7. Lv, Hualiang, Lai, Changchun, Zhao, Wenqu, Song, Yibo. 2022. GABPB1-AS1 acts as a tumor suppressor and inhibits non-small cell lung cancer progression by targeting miRNA-566/F-box protein 47. In Oncology research, 29, 401-409. doi:10.32604/or.2022.025262. https://pubmed.ncbi.nlm.nih.gov/37304650/