A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development

Dieter Riethmacher, Volker Brinkmanni, Carmen Birchmeier

Research output: Contribution to journalArticle

369 Citations (Scopus)

Abstract

The Ca2+-dependent cell adhesion molecule E-cadherin functions in the establishment and maintenance of epithelial cell morphology during embryogenesis and adult-hood. Downregulation or complete shut-down of E- cadherin expression and mutation of the gene are observed during the progression of tumors of epithelial origin (carcinomas) and correlate with the metastatic potential. We have introduced a targeted mutation into the E- cadherin gene by homologous recombination in mouse embryonic stem cells. The mutation removes E-cadherin sequences essential for Ca2+ binding and for adhesive function. These embryonic stem cells were used to generate mice carrying the mutation. Heterozygous mutant animals appear normal and are fertile. However, the homozygous mutation is not compatible with life: E- cadherin -/embryos show severe abnormalities before implantation. Particularly, the adhesive cells of the morula dissociate shortly after compaction has occurred, and their morphological polarization is then destroyed. Interestingly, the blastomers are still able to form desmosomes and tight junctions at sites of distorted cell-cell contact. Thus, maternal E-cadherin suffices for initial compaction of the morula but not for further preimplantation development to occur.

Original languageEnglish
Pages (from-to)855-859
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number3
DOIs
Publication statusPublished - Jan 31 1995
Externally publishedYes

Fingerprint

Cadherins
Mutation
Genes
Morula
Adhesives
Desmosomes
Tight Junctions
Homologous Recombination
Cell Adhesion Molecules
Embryonic Stem Cells
Embryonic Development
Down-Regulation
Embryonic Structures
Epithelial Cells
Maintenance
Mothers
Carcinoma
Gene Expression
Neoplasms

Keywords

  • cell adhesion
  • desmosome formation
  • maternal mRNA
  • morula decompaction
  • tight junction formation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. / Riethmacher, Dieter; Brinkmanni, Volker; Birchmeier, Carmen.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 3, 31.01.1995, p. 855-859.

Research output: Contribution to journalArticle

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