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To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR\/Cas9 system and identified potassium channel tetramerization domain containing 19 (\n                    <jats:italic>Kctd19<\/jats:italic>\n                    ) as an essential factor for meiosis. In prophase I,\n                    <jats:italic>Kctd19<\/jats:italic>\n                    deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of\n                    <jats:italic>Kctd19<\/jats:italic>\n                    KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the\n                    <jats:italic>Kctd19<\/jats:italic>\n                    KO phenotype with an epitope-tagged\n                    <jats:italic>Kctd19<\/jats:italic>\n                    transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of\n                    <jats:italic>Zfp541<\/jats:italic>\n                    KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009412","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T13:25:38Z","timestamp":1620393938000},"page":"e1009412","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male 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