Zfp541-KO Mouse

Zfp541, also known as SHIP1 (spermatogenic cell HDAC-interacting protein 1), is a germ-cell-specific gene essential for male meiosis and fertility [5]. It is involved in pathways related to chromatin organization and transcriptional regulation during spermatogenesis [1,2,4]. Mouse models are crucial for studying its function as they can mimic the in-vivo situation to understand its role in biological processes.

In Zfp541 knockout male mice, various defects occur. There are structural and recombination defects such as detached chromosome ends, abnormal localization of chromosome axis components and recombination proteins, and globally altered histone modifications [1]. Zfp541 -/- spermatocytes show abnormal programmed DNA double-strand break repair, impaired crossover formation and resolution, and asynapsis of the XY chromosomes, leading to meiotic arrest at the diplotene stage [2,3]. Additionally, Zfp541 deletion causes aberrant recruitment of DSB machinery to chromosome axes and generation of massive DSBs in late pachytene and diplotene spermatocytes [3].

In conclusion, Zfp541 is essential for male meiosis, acting as a key transcriptional regulator. It simultaneously regulates the transcription cascade and chromatin organization to ensure the coordinated progression of meiosis prophase I. The Zfp541 knockout mouse models have significantly contributed to understanding male infertility, as Zfp541 deficiency leads to various meiotic defects that can cause infertility [1-5].

References:

1. Zhou, Xu, Fang, Kailun, Liu, Yanlei, Chen, Charlie Degui, Wang, Shunxin. 2023. ZFP541 and KCTD19 regulate chromatin organization and transcription programs for male meiotic progression. In Cell proliferation, 57, e13567. doi:10.1111/cpr.13567. https://pubmed.ncbi.nlm.nih.gov/37921559/

2. Li, Yushan, Meng, Ranran, Li, Shanze, Xu, Dan, Wang, Fengchao. 2022. The ZFP541-KCTD19 complex is essential for pachytene progression by activating meiotic genes during mouse spermatogenesis. In Journal of genetics and genomics = Yi chuan xue bao, 49, 1029-1041. doi:10.1016/j.jgg.2022.03.005. https://pubmed.ncbi.nlm.nih.gov/35341968/

3. Xu, Jianze, Gao, Jianing, Liu, Junyan, Ma, Hui, Shi, Qinghua. . ZFP541 maintains the repression of pre-pachytene transcriptional programs and promotes male meiosis progression. In Cell reports, 38, 110540. doi:10.1016/j.celrep.2022.110540. https://pubmed.ncbi.nlm.nih.gov/35320728/

4. Horisawa-Takada, Yuki, Kodera, Chisato, Takemoto, Kazumasa, Araki, Kimi, Ishiguro, Kei-Ichiro. 2021. Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis. In Nature communications, 12, 3184. doi:10.1038/s41467-021-23378-4. https://pubmed.ncbi.nlm.nih.gov/34075040/

5. Choi, Eunyoung, Han, Cecil, Park, Inju, Eddy, Edward M, Cho, Chunghee. 2008. A novel germ cell-specific protein, SHIP1, forms a complex with chromatin remodeling activity during spermatogenesis. In The Journal of biological chemistry, 283, 35283-94. doi:10.1074/jbc.M805590200. https://pubmed.ncbi.nlm.nih.gov/18849567/