Fidgetin knockdown and knockout influences female reproduction distinctly in mice

J Biomed Res. 2022 Jul 10;36(4):269-279. doi: 10.7555/JBR.36.20220086.

Abstract

Microtubule-severing proteins (MTSPs), are a family of proteins which use adenosine triphosphate to sever microtubules. MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes. One member of this family, fidgetin ( FIGN), is also involved in male fertility; however, no studies have explored its roles in female fertility. In this study, we found mouse fidgetin is rich within oocyte zona pellucida (ZP) and is the only MTSP member to do so. Fidgetin also appears to interact with all three ZP proteins. These findings prompted us to propose that fidgetin might prevent polyspermy. Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy. We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies; however, female mice remained healthy and with normal fertility. Of all mouse MTSPs, only the mRNA level of fidgetin-like 1 ( FIGNL1) significantly increased. Therefore, we assert that fidgetin-like 1 compensates fidgetin's roles in fidgetin knockout female mice.

Keywords: female reproduction; fidgetin; knockdown; knockout; mouse.

Grants and funding

We thank all other lab members for their invaluable support and advice on the preparation of the manuscript. This work is financially supported by the National Natural Science Foundation of China (Grant No. 31671561) to Dong Zhang.