Meiosin-KO Mouse

Meiosin, also known as Meiosis initiator, is a DNA-binding protein and a germ-cell-specific transcription factor. It plays a central role in regulating the switch from mitosis to meiosis in mammalian germ cells, an essential process for spermatogenesis and oogenesis. Meiosin acts in collaboration with STRA8, and both are expressed in response to retinoic acid (RA) signaling, which is pivotal during meiotic initiation [1,2,4].

Functional analyses, including studies in mouse models, have revealed its crucial role. In a point-mutation mouse model with a homozygous missense variant in Meiosin (c.1735C>T, p.R579W), the meiotic prophase I program was impacted, and oocyte depletion was accelerated. The dual-luciferase reporter assay showed that this variant adversely affected the transcriptional function of Meiosin in upregulating meiotic genes. The variant in the high-mobility group (HMG) box domain disrupted the nuclear localization of the Meiosin protein, suggesting a unique role of this domain in meiosis initiation [3].

In conclusion, Meiosin is essential for meiotic initiation and subsequent meiotic prophase programs in both male and female germ cells. Mouse models with Meiosin variants have confirmed its role in regulating meiotic gene activation, and its dysfunction can lead to conditions like premature ovarian insufficiency, highlighting its significance in understanding human infertility [1,2,3].

References:

1. Ishiguro, Kei-Ichiro, Matsuura, Kumi, Tani, Naoki, Araki, Kimi, Niwa, Hitoshi. 2020. MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. In Developmental cell, 52, 429-445.e10. doi:10.1016/j.devcel.2020.01.010. https://pubmed.ncbi.nlm.nih.gov/32032549/

2. Ishiguro, Kei-Ichiro, Shimada, Ryuki. 2021. MEIOSIN directs initiation of meiosis and subsequent meiotic prophase program during spermatogenesis. In Genes & genetic systems, 97, 27-39. doi:10.1266/ggs.21-00054. https://pubmed.ncbi.nlm.nih.gov/34955498/

3. Zhang, Qian, Zhang, Wenzhe, Wu, Xinyi, Zhao, Shidou, Guo, Ting. . Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency. In Human reproduction (Oxford, England), 38, ii47-ii56. doi:10.1093/humrep/dead084. https://pubmed.ncbi.nlm.nih.gov/37982418/

4. Ishiguro, Kei-Ichiro. 2024. Mechanisms of meiosis initiation and meiotic prophase progression during spermatogenesis. In Molecular aspects of medicine, 97, 101282. doi:10.1016/j.mam.2024.101282. https://pubmed.ncbi.nlm.nih.gov/38797021/