First Author | Kiyozumi D | Year | 2018 |
Journal | Life Sci Alliance | Volume | 1 |
Issue | 5 | Pages | e201800064 |
PubMed ID | 30456378 | Mgi Jnum | J:279595 |
Mgi Id | MGI:6363599 | Doi | 10.26508/lsa.201800064 |
Citation | Kiyozumi D, et al. (2018) Laminin gamma1 C-terminal Glu to Gln mutation induces early postimplantation lethality. Life Sci Alliance 1(5):e201800064 |
abstractText | Laminin-integrin interactions regulate various adhesion-dependent cellular processes. gamma1C-Glu, the Glu residue in the laminin gamma1 chain C-terminal tail, is crucial for the binding of gamma1-laminins to several integrin isoforms. Here, we investigated the impact of gamma1C Glu to Gln mutation on gamma1-laminin binding to all possible integrin partners in vitro, and found that the mutation specifically ablated binding to alpha3, alpha6, and alpha7 integrins. To examine the physiological significance of gamma1C-Glu, we generated a knock-in allele, Lamc1 (EQ) , in which the gamma1C Glu to Gln mutation was introduced. Although Lamc1 (EQ/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 Lamc1 (EQ) allele on embryonic development, we developed a knock-in mouse strain enabling on-demand introduction of the gamma1C Glu to Gln mutation by the Cre-loxP system. The present study has revealed a crucial role of gamma1C-Glu-mediated integrin binding in postimplantation development and provides useful animal models for investigating the physiological roles of laminin-integrin interactions in vivo. |