{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:24:24Z","timestamp":1768965864782,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["311934"],"award-info":[{"award-number":["311934"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The loss of NHL repeat containing 2 (<jats:italic>Nhlrc2<\/jats:italic>) leads to early embryonic lethality in mice, but the exact timing is currently unknown. In this study, we determined the time of lethality for <jats:italic>Nhlrc2<\/jats:italic> knockout (KO), C57BL\/6NCrl\u2010<jats:italic>Nhlrc2<\/jats:italic><jats:sup>tm1a(KOMP)Wtsi<\/jats:sup>\/Oulu, embryos and the <jats:italic>in situ<\/jats:italic> expression pattern of <jats:italic>Nhlrc2<\/jats:italic> based on <jats:italic>LacZ<\/jats:italic> reporter gene expression during this period. <jats:italic>Nhlrc2<\/jats:italic> KO preimplantation mouse embryos developed normally after <jats:italic>in vitro<\/jats:italic> fertilization. Embryonic stem (ES) cells established from KO blastocysts proliferated normally despite a complete loss of the NHLRC2 protein. <jats:italic>Nhlrc2<\/jats:italic> KO embryos from timed matings implanted and were indistinguishable from their wildtype littermates on embryonic day (E) 6.5. On E7.5, <jats:italic>Nhlrc2<\/jats:italic> KO embryo development was arrested, and on E8.5, only 6% of the genotyped embryos were homozygous for the <jats:italic>Nhlrc2<\/jats:italic><jats:sup>tm1a(KOMP)Wtsi<\/jats:sup> allele. <jats:italic>Nhlrc2<\/jats:italic> KO E8.5 embryos showed limited embryonic or extraembryonic tissue differentiation and remained at the cylinder stage. <jats:italic>Nhlrc2<\/jats:italic> expression was ubiquitous but strongest in the epiblast\/ectoderm and extraembryonic ectoderm on E6.5 and E7.5. NHLRC2 is essential for early postimplantation development, and its loss leads to failed gastrulation and amniotic folding in mice. Future studies on the evolutionarily conserved NHLRC2 will provide new insights into the molecular pathways involved in the early steps of postimplantation development.<\/jats:p>","DOI":"10.1002\/dvg.23470","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:15:33Z","timestamp":1646738133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>Nhlrc2<\/i> is crucial during mouse gastrulation"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-6960","authenticated-orcid":false,"given":"Anniina E.","family":"Hiltunen","sequence":"first","affiliation":[{"name":"Medical Research Center Oulu and PEDEGO Research Unit University of Oulu and Oulu University Hospital  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reetta","family":"Vuolteenaho","sequence":"additional","affiliation":[{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veli\u2010Pekka","family":"Ronkainen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Miinalainen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Uusimaa","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu and PEDEGO Research Unit University of Oulu and Oulu University Hospital  Oulu Finland"},{"name":"Clinic for Children and Adolescents Pediatric Neurology Unit, Oulu University Hospital  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu and PEDEGO Research Unit University of Oulu and Oulu University Hospital  Oulu Finland"},{"name":"Department of Obstetrics and Gynecology Oulu University Hospital  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7642-4008","authenticated-orcid":false,"given":"Reetta","family":"Hinttala","sequence":"additional","affiliation":[{"name":"Medical Research Center Oulu and PEDEGO Research Unit University of Oulu and Oulu University Hospital  Oulu Finland"},{"name":"Biocenter Oulu University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202391"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-020-0776-0"},{"key":"e_1_2_7_4_1","unstructured":"Delhotal J. D. J.(2016). Characterization of NHLRC2 gene\u2010edited mice: a model for bovine developmental duplications. 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