Fbxo24-KO Mouse

Fbxo24, an F-box protein, is involved in multiple biological processes. It is part of the Skp-Cullin-F-box (SCF) ubiquitin E3 ligase machinery, which is crucial for protein ubiquitination and degradation, thus regulating various cellular functions and pathways [4,6].

In mice, disruption of Fbxo24 leads to significant phenotypes. Fbxo24 knockout (KO) mice exhibit abnormal accumulation of membraneless electron-dense granules in sperm flagella, malformed flagellar structures, impaired sperm motility, and male infertility, suggesting its essential role in spermatogenesis [1,5]. Also, Fbxo24 deficiency in mice causes abnormal mRNA alternative splicing in round spermatids, affecting genes related to sperm formation, leading to aberrant histone retention, incomplete axonemes, oversized chromatoid body, and abnormal mitochondrial coiling along sperm flagella, ultimately resulting in male sterility [3]. In the context of cancer, overexpression of Fbxo24 inhibits cell proliferation, migration, and invasion in H1299 cells by mediating the ubiquitin-dependent proteasomal degradation of PRMT6, which is aberrantly expressed in various cancers [4]. In breast cancer cells, FBXO24 functions as a tumor suppressor by ubiquitinating and degrading LSD1, an oncogenic chromatin modulator [2].

In conclusion, Fbxo24 is essential for normal sperm formation and male fertility as demonstrated by mouse KO models. It also plays a role in cancer-related processes such as cell proliferation. The study of Fbxo24 KO mouse models has provided valuable insights into male infertility and cancer-associated biological mechanisms, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Kaneda, Yuki, Miyata, Haruhiko, Xu, Zoulan, Emori, Chihiro, Ikawa, Masahito. 2024. FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility. In eLife, 13, . doi:10.7554/eLife.92794. https://pubmed.ncbi.nlm.nih.gov/39163107/

2. Dong, Bo, Song, Xiang, Wang, Xinzhao, Evers, B Mark, Wu, Yadi. . FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination. In Molecular cancer research : MCR, 21, 1303-1316. doi:10.1158/1541-7786.MCR-23-0169. https://pubmed.ncbi.nlm.nih.gov/37540490/

3. Li, Zhiming, Liu, Xingping, Zhang, Yan, Zhou, Liquan, Yuan, Shuiqiao. 2024. FBXO24 modulates mRNA alternative splicing and MIWI degradation and is required for normal sperm formation and male fertility. In eLife, 12, . doi:10.7554/eLife.91666. https://pubmed.ncbi.nlm.nih.gov/38470475/

4. Chen, Wei, Gao, Denghui, Xie, Long, Hong, An, Xiong, Sheng. 2020. SCF-FBXO24 regulates cell proliferation by mediating ubiquitination and degradation of PRMT6. In Biochemical and biophysical research communications, 530, 75-81. doi:10.1016/j.bbrc.2020.06.007. https://pubmed.ncbi.nlm.nih.gov/32828318/

5. Kaneda, Yuki, Miyata, Haruhiko, Xu, Zoulan, Emori, Chihiro, Ikawa, Masahito. 2024. FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.11.10.566635. https://pubmed.ncbi.nlm.nih.gov/37986737/

6. Chen, Wei, Xiong, Sheng, Li, Jin, Zou, Chunbin, Mallampalli, Rama K. 2015. The ubiquitin E3 ligase SCF-FBXO24 recognizes deacetylated nucleoside diphosphate kinase A to enhance its degradation. In Molecular and cellular biology, 35, 1001-13. doi:10.1128/MCB.01185-14. https://pubmed.ncbi.nlm.nih.gov/25582197/