University of Oulu

Hiltunen, A. E., Vuolteenaho, R., Ronkainen, V.-P., Miinalainen, I., Uusimaa, J., Lehtonen, S., & Hinttala, R. (2022). Nhlrc2 is crucial during mouse gastrulation. genesis, 60(3), e23470.

Nhlrc2 is crucial during mouse gastrulation

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Author: Hiltunen, Anniina E.1; Vuolteenaho, Reetta2; Ronkainen, Veli-Pekka2;
Organizations: 1Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Clinic for Children and Adolescents, Pediatric Neurology Unit, Oulu University Hospital, Oulu, Finland
4Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 18 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-06-08


The loss of NHL repeat containing 2 (Nhlrc2) leads to early embryonic lethality in mice, but the exact timing is currently unknown. In this study, we determined the time of lethality for Nhlrc2 knockout (KO), C57BL/6NCrl-Nhlrc2tm1a(KOMP)Wtsi/Oulu, embryos and the in situ expression pattern of Nhlrc2 based on LacZ reporter gene expression during this period. Nhlrc2 KO preimplantation mouse embryos developed normally after in vitro fertilization. Embryonic stem (ES) cells established from KO blastocysts proliferated normally despite a complete loss of the NHLRC2 protein. Nhlrc2 KO embryos from timed matings implanted and were indistinguishable from their wildtype littermates on embryonic day (E) 6.5. On E7.5, Nhlrc2 KO embryo development was arrested, and on E8.5, only 6% of the genotyped embryos were homozygous for the Nhlrc2tm1a(KOMP)Wtsi allele. Nhlrc2 KO E8.5 embryos showed limited embryonic or extraembryonic tissue differentiation and remained at the cylinder stage. Nhlrc2 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.

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Series: genesis
ISSN: 1526-954X
ISSN-E: 1526-968X
ISSN-L: 1526-954X
Volume: 60
Issue: 3
Article number: e23470
DOI: 10.1002/dvg.23470
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was conducted with support from the Academy of Finland profiling program (grant #311934), the Foundation for Pediatric Research, Finland, and State Grants for Health Research, Clinic for Children and Adolescents, and the Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.