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Based on our previous observations using single knockouts models and suggesting the existence of functional compensation among CRISP proteins, we investigated their relevance for male fertility by generating multiple\n                    <jats:italic>Crisp<\/jats:italic>\n                    gene mutants by CRISPR\/Cas9 technology. Whereas targeting of\n                    <jats:italic>Crisp1<\/jats:italic>\n                    and\n                    <jats:italic>Crisp3<\/jats:italic>\n                    yielded subfertile males with early embryo developmental defects, the same deletion in zygotes from fertile\n                    <jats:italic>\n                      Crisp2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      .Crisp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice led to the generation of both triple and quadruple knockout mice exhibiting a complete or severe disruption of male fertility due to a combination of sperm transport, fertilization, and embryo developmental defects linked to intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dysregulation. These observations reveal that CRISP proteins are essential for male fertility and organize in functional modules that contribute distinctly to fertility success, bringing insights into the mechanisms underlying functional redundancy\/compensation in protein families and emphasizing the importance of generating multiple and not just single knockout which might be masking the true functional relevance of family genes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202001406r","type":"journal-article","created":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T03:51:49Z","timestamp":1602301909000},"page":"15718-15733","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Functional redundancy and compensation: Deletion of multiple murine\n                    <i>Crisp<\/i>\n                    genes reveals their essential role for male fertility"],"prefix":"10.1096","volume":"34","author":[{"given":"L.","family":"Curci","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (IByME\u2010CONICET) Ciudad Aut\u00f3noma de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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