Laminin γ1 c-terminal Glu to Gln mutation induces early postimplantation lethality

Daiji Kiyozumi, Yukimasa Taniguchi, Itsuko Nakano, Junko Toga, Emiko Yagi, Hidetoshi Hasuwa, Masahito Ikawa, Kiyotoshi Sekiguchi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Laminin–integrin interactions regulate various adhesion-dependent cellular processes. γ1C-Glu, the Glu residue in the laminin γ1 chain C-terminal tail, is crucial for the binding of γ1-laminins to several integrin isoforms. Here, we investigated the impact of γ1C Glu to Gln mutation on γ1-laminin binding to all possible integrin partners in vitro, and found that the mutation specifically ablated binding to α3, α6, and α7 integrins. To examine the physiological significance of γ1C-Glu, we generated a knock-in allele, Lamc1EQ, in which the γ1C Glu to Gln mutation was introduced. Although Lamc1EQ/EQ homozygotes developed into blastocysts and deposited laminins in their basement membranes, they died just after implantation because of disordered extraembryonic development. Given the impact of the Lamc1EQ allele on embryonic development, we developed a knock-in mouse strain enabling on-demand introduction of the γ1C Glu to Gln mutation by the Cre-loxP system. The present study has revealed a crucial role of γ1C-Glu–mediated integrin binding in postimplantation development and provides useful animal models for investigating the physiological roles of laminin–integrin interactions in vivo.

Original languageEnglish
Article numbere201800064
JournalLife Science Alliance
Volume1
Issue number5
DOIs
Publication statusPublished - 2018 Jan 1

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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    Kiyozumi, D., Taniguchi, Y., Nakano, I., Toga, J., Yagi, E., Hasuwa, H., Ikawa, M., & Sekiguchi, K. (2018). Laminin γ1 c-terminal Glu to Gln mutation induces early postimplantation lethality. Life Science Alliance, 1(5), [e201800064]. https://doi.org/10.26508/lsa.201800064