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Role for Sez12 in migration of cranial neural crest cells

Research Project

Project/Area Number 10671714
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionTokai University

Principal Investigator

KAJIWARA Kagemasa  Tokai University Institute of Medical Sciences Assistant Professor, 総合医学研究所, 講師 (00204397)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsDiGeorge syndrome / c-Ets1 / craniofacial development / Sez12 / retinoic acid / gene targeting / ganglioside / ノックアウトマウス / 神経冠細胞
Research Abstract

SEZ-12 is a seizure-related mouse cDNA whose expression level is down-regulated by a convulsant drug, pentylenetetrazol, both in cultured cerebral neurons and in adult brain. Sequence analysis of SEZ-12 shows a significant homology to a human cDNA, named DGCR2/IDD/LAN, isolated from the chromosome 22q11.2 region critical for the DiGeorge syndrome. Here we determined the chromosomal localization of SEZ-12 gene, Sez12, by interspecific backcross analysis. Sez12 mapped on the proximal region of mouse chromosome 16 homologous to the human chromosome 22q11. RNA blotting and whole mount in situ hybridization of Sez12 mRNA showed a relative abundance in craniofacial region during mouse embryogenesis. To further determine the molecular mechanism underlying this expression, the deletion constructs of the Sez12 promoter were transfected into NIH3T3 cells. The results revealed an essential domain (-180 to -1) which included a cis-acting element for the transcription factor c-Ets1 and was upregulated its transcriptional activity by retinoic acid. Moreover, we showed that Sez12 products expressed in Xenopus oocytes were induced a large inward current by extracellular application of an oligosaccharide ligand, ganglioside glycolipid, suggesting that the Sez12 protein is a key effector whose interaction with some cell-surface ligands result in normal cellular development during embryogenesis. Taken together, Sez12 may play an important role in craniofacial development and that haploinsufficiency of this human homologue may be related in part to pathogenesis of DiGeorge syndrome. Now, to directly understand the physiological role of Sez12 in the animal, a null mutation has been introduced into the gene by homologous recombination in mouse embryonic stem cells.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Shigeharu Wakana: "Gene mapping of SEZ group genes and determination of pentylenetetrazol susceptible quantitative trait loci in the mouse chromosome"Brain Research. 857. 286-290 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kengo Tomita: "Gene structure and promoter for Crad2 encoding mouse cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme"Gene. 251. 175-186 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kiyoko Kawamura: "The error-prone DNA polymerase zeta catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues"Int.J.Oncol.. 18. 97-103 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kagemasa Kajiwara: "Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis"Genes to Cells. 6(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakana, S., Sugaya, E., Naramoto, F., Yokote, N., Maruyama, C., Jin, W., Ohguchi, H., Tsuda, T., Sugaya, A., and Kajiwara, K.: "Gene mapping of SEZ group genes and determination of pentylenetetrazol susceptible quantitative trait loci in the mouse chromosome"Brain Res.. 857. 286-290 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tomita, K., Sato, M., Kajiwara, K., Tanaka, M., Tamiya, G., Makino, S., Tomizawa, M., Mizutani, A., Kuwano, Y., Shiina, T., Ishii, H., and Kimura, M.: "Gene structure and promoter for Crad2 encoding mouse cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme"Gene.. 251. 175-186 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamura, K., J,O.W., Bahar, R., Koshikawa, N., Shishikura, T., Nakagawara, A., Sakiyama, S., Kajiwara, K., Kimura, M., and Tagawa, M.: "The error-prone DNA polymerase zeta catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues."Int J Oncol.. 18. 97-103 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kajiwara, K., O-Wang, J., Sakurai, T., Yamashita, S., Tanaka, M., Sato, M., Tagawa, M., Sugaya, E., Nakamura, K., Nakao, K., Katsuki, M., and Kimura, M.: "Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis."Genes Cells.. 6 (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kengo Tomita: "Gene structure and promoter for Crad2 encoding mouse cisretinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme"Gene. 251. 175-186 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kiyoko Kawamura: "The error-prone DNA polymerase zeta catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues"Int.J Oncol.. 18. 97-103 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kagemasa Kajiwara: "Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis"Genes to Cells. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeharu Wakana: "Gene mapping of SEZ group genes and determination of pentylenetetrazole susceptible quantitative trait loci in the mouse chromosome"Brain Research. (印刷中).

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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