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 language | English |
|---|---|
| Pages (from-to) | 855-859 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 92 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 31 1995 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development
AU - Riethmacher, Dieter
AU - Brinkmanni, Volker
AU - Birchmeier, Carmen
PY - 1995/1/31
Y1 - 1995/1/31
N2 - 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.
AB - 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.
KW - cell adhesion
KW - desmosome formation
KW - maternal mRNA
KW - morula decompaction
KW - tight junction formation
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U2 - 10.1073/pnas.92.3.855
DO - 10.1073/pnas.92.3.855
M3 - Article
VL - 92
SP - 855
EP - 859
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 3
ER -