Fam111a-KO Mouse

Fam111a, also known as family with sequence similarity 111 member A, is a nuclear protein with a trypsin-like protease domain. It plays crucial roles in regulating host DNA replication, facilitating efficient activation of DNA replication origins [2]. It is also involved in protecting replication forks from protein obstacles like poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes, and has been associated with maintaining genome integrity [5]. Additionally, it functions as an antiviral factor against certain viruses, such as vaccinia virus (VACV) [1,4].

In functional studies, deletion of Fam111a in cell models rescued the replication of VACV-ΔSPI-1 and modified VACV Ankara (MVA), while its overexpression reduced viral DNA replication and virus titers [1]. In mice, Fam111a knockout (Fam111a-/-) mice displayed normal electrolyte homeostasis, indicating that Fam111a is dispensable for this function [3].

In conclusion, Fam111a is essential for DNA replication-related processes and antiviral defense. The use of Fam111a knockout mouse models has provided insights into its non-essential role in electrolyte homeostasis, highlighting its diverse functions in different biological contexts [1,2,3,5].

References:

1. Zhu, Junda, Gao, Xintao, Li, Yijing, Wu, Wenxue, Peng, Chen. 2023. Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2304242120. doi:10.1073/pnas.2304242120. https://pubmed.ncbi.nlm.nih.gov/37607234/

2. Rios-Szwed, Diana O, Alvarez, Vanesa, Sanchez-Pulido, Luis, Lamond, Angus, Alabert, Constance. 2023. FAM111A regulates replication origin activation and cell fitness. In Life science alliance, 6, . doi:10.26508/lsa.202302111. https://pubmed.ncbi.nlm.nih.gov/37793778/

3. Ilenwabor, Barnabas P, Schigt, Heidi, Kompatscher, Andreas, Hoenderop, Joost G J, de Baaij, Jeroen H F. 2022. FAM111A is dispensable for electrolyte homeostasis in mice. In Scientific reports, 12, 10211. doi:10.1038/s41598-022-14054-8. https://pubmed.ncbi.nlm.nih.gov/35715480/

4. Naicker, Danielle, Rhoda, Cenza, Sunda, Falone, Arowolo, Afolake. 2024. Unravelling the Intricate Roles of FAM111A and FAM111B: From Protease-Mediated Cellular Processes to Disease Implications. In International journal of molecular sciences, 25, . doi:10.3390/ijms25052845. https://pubmed.ncbi.nlm.nih.gov/38474092/

5. Kojima, Yusuke, Machida, Yuka, Palani, Sowmiya, Kaufmann, Scott H, Machida, Yuichi J. 2020. FAM111A protects replication forks from protein obstacles via its trypsin-like domain. In Nature communications, 11, 1318. doi:10.1038/s41467-020-15170-7. https://pubmed.ncbi.nlm.nih.gov/32165630/