Abnormalities of developmental cell death in Dad1-deficient mice

Kiyomasa Nishii, Teruhisa Tsuzuki, Madoka Kumai, Naoki Takeda, Hideya Koga, Shinichi Aizawa, Takeharu Nishimoto, Yosaburo Shibata

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Dad1, the defender against apoptotic cell death, comprises the oligosaccharyltransferase complex and is well conserved among eukaryotes. In hamster BHK21-derived tsBN7 cells, loss of Dad1 causes apoptosis which cannot be prevented by Bcl-2. Results: To determine the role of Dad1 function in vivo, we prepared by gene targeting, mice harbouring a disrupted Dad1 gene. Homozygous mutants died shortly after they were implanted with the characteristic features of apoptosis. In an in vitro blastocyst culture system, Dad1-null cells displayed abnormalities which were comparable to those obtained in vivo. However, oligosaccharyltransferase activity was apparently retained even after the Dad1-null cells were destined to die. Some live-born heterozygous mutants displayed soft-tissue syndactyly. Mild thymic hypoplasia was also indicated in heterozygotes. Conclusion: These results suggest the involvement of the Dad1 gene in the acquisition of a common syndactyly phenotype, as well as in the control of programmed cell death during development.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalGenes to Cells
Volume4
Issue number4
DOIs
Publication statusPublished - Jun 5 1999

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Syndactyly
Null Lymphocytes
Cell Death
Apoptosis
Gene Targeting
Blastocyst
Heterozygote
Eukaryota
Cricetinae
Genes
Phenotype
dolichyl-diphosphooligosaccharide - protein glycotransferase
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Nishii, K., Tsuzuki, T., Kumai, M., Takeda, N., Koga, H., Aizawa, S., ... Shibata, Y. (1999). Abnormalities of developmental cell death in Dad1-deficient mice. Genes to Cells, 4(4), 243-252. https://doi.org/10.1046/j.1365-2443.1999.00256.x

Abnormalities of developmental cell death in Dad1-deficient mice. / Nishii, Kiyomasa; Tsuzuki, Teruhisa; Kumai, Madoka; Takeda, Naoki; Koga, Hideya; Aizawa, Shinichi; Nishimoto, Takeharu; Shibata, Yosaburo.

In: Genes to Cells, Vol. 4, No. 4, 05.06.1999, p. 243-252.

Research output: Contribution to journalArticle

Nishii, K, Tsuzuki, T, Kumai, M, Takeda, N, Koga, H, Aizawa, S, Nishimoto, T & Shibata, Y 1999, 'Abnormalities of developmental cell death in Dad1-deficient mice', Genes to Cells, vol. 4, no. 4, pp. 243-252. https://doi.org/10.1046/j.1365-2443.1999.00256.x
Nishii K, Tsuzuki T, Kumai M, Takeda N, Koga H, Aizawa S et al. Abnormalities of developmental cell death in Dad1-deficient mice. Genes to Cells. 1999 Jun 5;4(4):243-252. https://doi.org/10.1046/j.1365-2443.1999.00256.x
Nishii, Kiyomasa ; Tsuzuki, Teruhisa ; Kumai, Madoka ; Takeda, Naoki ; Koga, Hideya ; Aizawa, Shinichi ; Nishimoto, Takeharu ; Shibata, Yosaburo. / Abnormalities of developmental cell death in Dad1-deficient mice. In: Genes to Cells. 1999 ; Vol. 4, No. 4. pp. 243-252.
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