Rbpms2-KO Mouse

Rbpms2, an RNA-binding protein, is a member of the RNA-recognition-motif-containing protein family. It plays crucial roles in multiple biological processes. In the heart, it is a myocardial-enriched splicing regulator essential for cardiac function, involving in myofibril organization and calcium handling [1]. In zebrafish, it acts as a binary fate-switch in early gonocytes, promoting female fate by repressing testis factors and promoting oocyte factors through the mTorc1 signaling pathway [2,4].

Gene knockout studies have been instrumental in revealing its functions. Zebrafish rbpms2 knockout embryos display early cardiac dysfunction with reduced ejection fraction, myofibril disarray, and calcium handling abnormalities, similar phenotypes are also seen in RBPMS2-deficient human cardiomyocytes [1]. In zebrafish, rbpms2 mutants initially have early oocytes, but definitive oogenesis fails during sexual differentiation, and they develop as fertile males [3]. In mouse, maternal RBPMS2 knockdown inhibits embryo development from the morula to the blastocyst stage by impairing the BMP pathway and E-cadherin localization [5]. In Japanese flounder, siRNA interference and overexpression of Rbpms2 in gonadal primary cells showed its role in repressing male-related genes and promoting female-related genes [6].

In summary, Rbpms2 is essential for cardiac function, sexual differentiation in zebrafish and Japanese flounder, and early mouse embryo development. The gene knockout models in different species have significantly contributed to understanding its functions in these biological processes, providing insights into potential mechanisms underlying heart diseases and reproductive disorders.

References:

1. Akerberg, Alexander A, Trembley, Michael, Butty, Vincent, Burns, Caroline E, Burns, C Geoffrey. 2022. RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function. In Circulation research, 131, 980-1000. doi:10.1161/CIRCRESAHA.122.321728. https://pubmed.ncbi.nlm.nih.gov/36367103/

2. Wilson, Miranda L, Romano, Shannon N, Khatri, Nitya, Draper, Bruce W, Marlow, Florence L. 2024. Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component Mios. In Nature communications, 15, 5248. doi:10.1038/s41467-024-49613-2. https://pubmed.ncbi.nlm.nih.gov/38898112/

3. Kaufman, Odelya H, Lee, KathyAnn, Martin, Manon, Rothhämel, Sophie, Marlow, Florence L. 2018. rbpms2 functions in Balbiani body architecture and ovary fate. In PLoS genetics, 14, e1007489. doi:10.1371/journal.pgen.1007489. https://pubmed.ncbi.nlm.nih.gov/29975683/

4. Wilson, Miranda L, Romano, Shannon N, Khatri, Nitya, Draper, Bruce W, Marlow, Florence L. 2024. Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component, Mios. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.01.25.577235. https://pubmed.ncbi.nlm.nih.gov/38328218/

5. Zhou, Cheng, Zheng, Lu, Teng, Hui, Chen, Li, Yao, Bing. 2023. Maternal RNA binding protein with multiple splicing 2 (RBPMS2) is involved in mouse blastocyst formation through the bone morphogenetic protein pathway. In Reproductive biomedicine online, 47, 103238. doi:10.1016/j.rbmo.2023.05.010. https://pubmed.ncbi.nlm.nih.gov/37573751/

6. Liu, Cui, Zhang, Longsheng, Xia, You, Wu, Jikui, Zhang, Junling. 2024. Identification, expression, and function analysis of Rbpms2 splicing variants in Japanese flounder gonad. In General and comparative endocrinology, 359, 114628. doi:10.1016/j.ygcen.2024.114628. https://pubmed.ncbi.nlm.nih.gov/39414089/