Kctd19-KO Mouse

Kctd19, or potassium channel tetramerization domain containing 19, is an essential factor for meiosis, a crucial cell division process in sexual reproduction. It is associated with the ZFP541-HDAC1 complex and is involved in regulating meiotic progression, thus playing a vital role in male fertility [1,4,5,8]. Gene knockout mouse models have been valuable in studying its function [1,2,3,4,5,6,7,8,9].

In Kctd19 knockout male mice, spermatocytes undergo apoptotic elimination during the metaphase-anaphase transition in meiosis, despite normal synapsis and DNA damage response in prophase I [1]. Mouse models mimicking human Kctd19 variants also show meiotic metaphase I arrest due to severely disrupted chromosome individualization [2]. Biallelic missense variants in Kctd19 in infertile human males lead to abnormal sperm head morphology, immature nuclei, and nuclear aneuploidy, and similar variants in mice cause infertility due to meiotic arrest [3]. Depletion of Kctd19 in male mice delays pachytene progression, and studies suggest that ZFP541/Kctd19 complex activates meiotic genes and modulates chromatin organization during meiosis prophase I [4,5].

In conclusion, Kctd19 is essential for meiosis and male fertility. Through gene knockout mouse models, we've learned that it plays a critical role in regulating meiotic progression, chromosome individualization, and chromatin organization. Understanding Kctd19's function contributes to the study of male infertility, a disease area where its variants have been linked to non-obstructive azoospermia and oligoasthenoteratozoospermia [1,2,3,7].

References:

1. Oura, Seiya, Koyano, Takayuki, Kodera, Chisato, Ishiguro, Kei-Ichiro, Ikawa, Masahito. 2021. KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice. In PLoS genetics, 17, e1009412. doi:10.1371/journal.pgen.1009412. https://pubmed.ncbi.nlm.nih.gov/33961623/

2. Liu, Junyan, Rahim, Fazal, Zhou, Jianteng, Zhang, Huan, Shi, Qinghua. 2023. Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans. In iScience, 26, 107193. doi:10.1016/j.isci.2023.107193. https://pubmed.ncbi.nlm.nih.gov/37485353/

3. Wang, Weili, Su, Lilan, Meng, Lanlan, Tu, Chaofeng, Tan, Yue-Qiu. . Biallelic variants in KCTD19 associated with male factor infertility and oligoasthenoteratozoospermia. In Human reproduction (Oxford, England), 38, 1399-1411. doi:10.1093/humrep/dead095. https://pubmed.ncbi.nlm.nih.gov/37192818/

4. 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/

5. 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/

6. Zhang, Yan, Huang, Xuzhao, Xu, Qiaoqiao, Xia, Yankai, Zhang, Feng. 2023. Homozygous nonsense variants of KCTD19 cause male infertility in humans and mice. In Journal of genetics and genomics = Yi chuan xue bao, 50, 615-619. doi:10.1016/j.jgg.2023.05.008. https://pubmed.ncbi.nlm.nih.gov/37257643/

7. Muranishi, Yuki, Katoh-Fukui, Yuko, Hattori, Atsushi, Shinohara, Nobuo, Fukami, Maki. 2024. Compound heterozygous KCTD19 variants in a man with isolated nonobstructive azoospermia. In Reproductive medicine and biology, 23, e12608. doi:10.1002/rmb2.12608. https://pubmed.ncbi.nlm.nih.gov/39318590/

8. 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/

9. Fang, Kailun, Li, Qidan, Wei, Yu, Liu, Siqi, Chen, Charlie Degui. 2021. Prediction and Validation of Mouse Meiosis-Essential Genes Based on Spermatogenesis Proteome Dynamics. In Molecular & cellular proteomics : MCP, 20, 100014. doi:10.1074/mcp.RA120.002081. https://pubmed.ncbi.nlm.nih.gov/33257503/