Meikin-KO Mouse

Meikin, also known as Moa1 in fission yeast and Spo13 in yeast, is a conserved meiosis-specific kinetochore regulator. It plays a central role in establishing meiosis-specific kinetochore function, regulating mono-orientation of sister chromatids and centromeric cohesion protection during meiosis I. These functions are crucial for accurate chromosome segregation in germ cells, ensuring the generation of haploid gametes [1,2,3,5].

In mouse oocytes, mutations preventing Meikin cleavage or conditionally inactivating Meikin at anaphase I lead to defective meiosis II chromosome alignment, indicating its importance in proper meiotic progression [4]. In fission yeast, Moa1 (Meikin) recruits Plo1 (polo-like kinase) to kinetochores, phosphorylates Spc7 (KNL1) to accumulate Bub1, which is important for robust Sgo1 (shugoshin) localization and cohesion protection at centromeres [6]. Also, in mouse, MEIKIN is a maternal protein highly expressed before metaphase I, and its degradation and C-terminal phosphorylation by PLK1 are critical for the metaphase-anaphase transition in meiotic oocytes. Suppression of MEIKIN degradation causes chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest [3].

In conclusion, Meikin is essential for meiosis-specific chromosome segregation processes. Studies using mouse models, especially those with Meikin inactivation or mutation, have revealed its significance in preventing meiotic abnormalities, which is relevant to understanding infertility, abortion, and other diseases related to oocyte meiotic maturation failure and chromosome abnormalities [3,4].

References:

1. Ma, Wei, Zhou, Jingwen, Chen, Jian, Carr, Antony M, Watanabe, Yoshinori. 2021. Meikin synergizes with shugoshin to protect cohesin Rec8 during meiosis I. In Genes & development, 35, 692-697. doi:10.1101/gad.348052.120. https://pubmed.ncbi.nlm.nih.gov/33888556/

2. Rojas, Julie, Oz, Tugce, Jonak, Katarzyna, Biriuk, Olha, Zachariae, Wolfgang. 2023. Spo13/MEIKIN ensures a Two-Division meiosis by preventing the activation of APC/CAma1 at meiosis I. In The EMBO journal, 42, e114288. doi:10.15252/embj.2023114288. https://pubmed.ncbi.nlm.nih.gov/37728253/

3. Fan, Li-Hua, Qi, Shu-Tao, Wang, Zhen-Bo, Sun, Qing-Yuan, Ou, Xiang-Hong. 2024. MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte. In Histochemistry and cell biology, 162, 447-464. doi:10.1007/s00418-024-02316-7. https://pubmed.ncbi.nlm.nih.gov/39093409/

4. Maier, Nolan K, Ma, Jun, Lampson, Michael A, Cheeseman, Iain M. 2021. Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition. In Developmental cell, 56, 2192-2206.e8. doi:10.1016/j.devcel.2021.06.019. https://pubmed.ncbi.nlm.nih.gov/34331869/

5. Kim, Jihye, Ishiguro, Kei-ichiro, Nambu, Aya, Sakuno, Takeshi, Watanabe, Yoshinori. 2014. Meikin is a conserved regulator of meiosis-I-specific kinetochore function. In Nature, 517, 466-71. doi:10.1038/nature14097. https://pubmed.ncbi.nlm.nih.gov/25533956/

6. Miyazaki, Seira, Kim, Jihye, Yamagishi, Yuya, Sakuno, Takeshi, Watanabe, Yoshinori. 2017. Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I. In Genes to cells : devoted to molecular & cellular mechanisms, 22, 552-567. doi:10.1111/gtc.12496. https://pubmed.ncbi.nlm.nih.gov/28497540/