Zcwpw1-KO Mouse
一般名
Zcwpw1-KO
製品ID
S-KO-09795
背景情報
C57BL/6NCya
系統ID
KOCMP-381678-Zcwpw1-B6N-VA
状況
このマウス系統を論文で使用する場合は、「Zcwpw1-KO Mouse（カタログ番号S-KO-09795）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
標準的な配送方法では、少なくとも3匹のヘテロ接合体キャリアを保証しています。ホモ接合体キャリアや指定された性別の個体の繁殖サービスも利用可能です。
基本情報
系統名
Zcwpw1-KO
系統ID
KOCMP-381678-Zcwpw1-B6N-VA
遺伝子名
製品ID
S-KO-09795
遺伝子別名
Gm1053
遺伝子別名
C57BL/6NCya
NCBI ID
修正
Conventional knockout
染色体
Chr 5
表現型
アプリケーション
--
さらに
系統詳細
EnsemblトランスクリプトID
ENSMUST00000035852
NCBIトランスクリプトID
NM_001005426
ターゲット領域
Exon 3~5
有効領域の大きさ
~3.0 kb
遺伝子研究の概要
Zcwpw1, lacking common aliases as per the references, is a gene with crucial functions in meiosis. It contains H3K4me3 and H3K36me3 recognition domains and is recruited to recombination hotspots by PRDM9, playing a vital role in meiotic double-strand break repair. This process is essential for homologous chromosome pairing, genetic diversity, and the formation of haploid germ cells [2,3,4,5,7].
Male Zcwpw1 knockout mice show severe DSB repair and synapsis defects, with persistent DMC1 foci, leading to downstream sterility. Spermatocytes in these mice are arrested at the pachytene-like stage, phenocopying Zcwpw1-knockout mice. This indicates Zcwpw1 is indispensable for meiosis synapsis in males [2,3,4]. In contrast, in female mice, deletion of Zcwpw1 only slows down meiosis prophase I progression, and Zcwpw1 -/- female mice have normal fertility until mid-adulthood [4]. A loss-of-function variant in ZCWPW1 in humans has also been associated with male infertility, presenting with sperm head defects and high DNA fragmentation [8]. Additionally, Zcwpw1 has been linked to Alzheimer's disease as a potential risk gene, with rare-variant burden highlighting its possible role in the disease [1,6,9].
In summary, Zcwpw1 is essential for meiotic double-strand break repair and synapsis in male meiosis, playing a key role in male fertility. The gene knockout mouse models have clearly demonstrated its function in male reproductive processes. The association with Alzheimer's disease also indicates its potential importance in neurodegenerative disease research, although further exploration is needed to fully understand its role in this context.
References:
1. Karch, Celeste M, Goate, Alison M. 2014. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. In Biological psychiatry, 77, 43-51. doi:10.1016/j.biopsych.2014.05.006. https://pubmed.ncbi.nlm.nih.gov/24951455/
2. Wells, Daniel, Bitoun, Emmanuelle, Moralli, Daniela, Green, Catherine, Myers, Simon R. 2020. ZCWPW1 is recruited to recombination hotspots by PRDM9 and is essential for meiotic double strand break repair. In eLife, 9, . doi:10.7554/eLife.53392. https://pubmed.ncbi.nlm.nih.gov/32744506/
3. Huang, Tao, Yuan, Shenli, Gao, Lei, Chen, Zi-Jiang, Liu, Hongbin. 2020. The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair. In eLife, 9, . doi:10.7554/eLife.53459. https://pubmed.ncbi.nlm.nih.gov/32374261/
4. Li, Miao, Huang, Tao, Li, Meng-Jing, Liu, Hong-Bin, Liu, Kui. 2019. The histone modification reader ZCWPW1 is required for meiosis prophase I in male but not in female mice. In Science advances, 5, eaax1101. doi:10.1126/sciadv.aax1101. https://pubmed.ncbi.nlm.nih.gov/31453335/
5. Yuan, Shenli, Huang, Tao, Bao, Ziyou, Liu, Hongbin, Chen, Zi-Jiang. 2022. The histone modification reader ZCWPW1 promotes double-strand break repair by regulating cross-talk of histone modifications and chromatin accessibility at meiotic hotspots. In Genome biology, 23, 187. doi:10.1186/s13059-022-02758-z. https://pubmed.ncbi.nlm.nih.gov/36068616/
6. Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Bellenguez, Céline, Lambert, Jean-Charles. 2022. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease. In Nature genetics, 54, 1786-1794. doi:10.1038/s41588-022-01208-7. https://pubmed.ncbi.nlm.nih.gov/36411364/
7. Mahgoub, Mohamed, Paiano, Jacob, Bruno, Melania, Nussenzweig, André, Macfarlan, Todd S. 2020. Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice. In eLife, 9, . doi:10.7554/eLife.53360. https://pubmed.ncbi.nlm.nih.gov/32352380/
8. Song, Yuelin, Guo, Juncen, Zhou, Yanling, Zhang, Guohui, Wang, Hongjing. 2024. A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation. In Reproductive health, 21, 18. doi:10.1186/s12978-024-01746-9. https://pubmed.ncbi.nlm.nih.gov/38310235/
9. Kim, Jong Hun. 2019. Genetics of Alzheimer's Disease. In Dementia and neurocognitive disorders, 17, 131-136. doi:10.12779/dnd.2018.17.4.131. https://pubmed.ncbi.nlm.nih.gov/30906402/
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