title: β-catenin-mediated adhesion is required for successful preimplantation mouse embryo development.
abstract: β-catenin (CTNNB1) is integral to cell adhesion and to the canonical Wnt signaling pathway. The effects of maternal and zygotic CTNNB1 on embryogenesis have each been separately assessed, whereas the effect of its total absence has not. As the 'traditional' conditional Ctnnb1 knockout alleles give rise to truncated CTNNB1 fragments, we designed a new knockout allele incapable of CTNNB1 production. Mouse embryos lacking intact maternal/zygotic CTNNB1 from two knockout strains were examined in detail. Preimplantation embryos are formed, yet abnormalities in their size and shape were found throughout pre- and early postimplantation development. In the absence of the zona pellucida, embryos lacking CTNNB1 undergo fission and these separated blastomeres can become small trophoblastic vesicles, which in turn induce decidual reactions. Comparing the severity of this defective adhesion phenotype in embryos bearing the null allele with those carrying the 'traditional' knockout allele suggests a hypomorphic effect of the truncated CTNNB1 protein fragment, an important observation with possible impact on previous and future studies.
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore Institute of Molecular and Cellular Biology, A*STAR, Proteos 5-02, 138673, Singapore.
authors.forename: Daniel
authors.initials: D
authors.lastname: Messerschmidt
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Wilhelmine N
authors.initials: WN
authors.lastname: de Vries
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok, 10170 Thailand.
authors.forename: Chanchao
authors.initials: C
authors.lastname: Lorthongpanich
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore Nanyang Polytechnic, School of Chemical and Life Sciences, 569830, Singapore.
authors.forename: Sathish
authors.initials: S
authors.lastname: Balu
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok, 10170 Thailand.
authors.forename: Davor
authors.initials: D
authors.lastname: Solter
authors.affiliation: Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos 06-06, 138648, Singapore The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok, 10170 Thailand bbk4@me.com.
authors.forename: Barbara B
authors.identifier: 0000-0002-2597-5619
authors.initials: BB
authors.lastname: Knowles
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion; D047108:Embryonic Development; D017353:Gene Deletion; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000378:metabolism; D015053:Zygote / Q000378:metabolism; D051176:beta Catenin / Q000172:deficiency / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D051176:beta Catenin
keywords: Blastocyst; Ctnnb1tm1Knw; Mammalian embryogenesis; Maternal/zygotic; Null phenotype; Peri-implantation; Preimplantation; Truncated CTNNB1; β-catenin allele