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1994 Fiscal Year Final Research Report Summary

PRODUCTION OF MOUSE MODELS FOR MALFORMATION BY GENE TRAP

Research Project

Project/Area Number 04454578
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

YAMAMURA Kenichi  KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (90115197)

Co-Investigator(Kenkyū-buntansha) ARAKI Kimi  KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 助手 (90211705)
Project Period (FY) 1992 – 1994
KeywordsES CELL / GENE TRAP / MORPHOGENESIS / MODEL MOUSE
Research Abstract

A strategy to monitor transcriptionally active regions of the genome was first described in bacteria in 1979. It involves the introdution of reporter into the genome that require the acquisition of cis-acting DNA sequences to activate reporter gene expression. This approach has been applied more recently in higher organisms using modified vectors suitable for eukaryotic transcription units. In the mouse unknown genes have been identified by insertional mutation in transgenic mice generated by retroviral infection or DNA microinjection. However, this approach is laborious and time-consuming. Through the use of embryonic stem (ES) cells, the enhancer traps as well as the gene trap are now possible in the mouse. In the trap vector bacterial lacZ gene is usually used as a reporter gene. However, this gene product is thought to exert toxic effect on certain types of cell. We fpoud that this toxicity was reduced by the target expression of b-galactosidase in the nucleus. Using the gene trap method, we demonstrated that new genes were identified in about 60% ES trap clones, and that the 3'region of flanking mouse genome was deleted of rearranged by insertion event in most of cases. We isolated 6 ES trap clones that showed expression of lacZ before induction of differentiatio by retinoic acid. The promoter region of the unknown gene, termed Ayul, was isolated from one of these trap clones. This gene is expressed in the nerve cell of brain, epithelial cells of sstomach and duodenum, and testis of adult mouse. b-galactosidase activity was also detected in the midgut of 8.5 day embry when the gastro-intesitinal tract starts to form, suggesting that the Ayul gene is involved in the formation of gastro-intestinal tract.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nishiyori,A.et al.: "Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors" J.Biol.Chem.269. 1323-1331 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toyonaga T.et al.: "Chronic active hepatitis in transgenic mice expressing interferon-γ in the liver" Proc.Natl.Acad.Sci.USA.91. 614-618 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaname,T.et al.: "The upstream sequence of a new growth/differebtiation factor,midkine(MK),mediates developmentally regulated lacZ gene expression in transgenic mice" Develp.Growth Differ.36. 231-238 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyama,T.et al.: "Exprssion of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice" Gene. 141. 187-192 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mantani,A.et al.: "A novel isoform of the neurofibromatosis type-1 mRNA and a switch of isoforms during murine cell differentiation and proliferation" Gene. 148. 245-251 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,S.et al.: "Improvement of germ line transmission by targeting b-galactosidase to nuclei in transgeic mice" Develop.Growth Differ.36. 521-527 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suematsu.S.,Yamamura,K.et al.: "Generation of plasmacytomas with the chromosomal trans-location t(12;15)interleukin 6 trangenic mice." Proc Natl Acad Sci USA. 89. 232-235 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao,X.,Yamamura,K.et al.: "Developmental and liver-specific expression directed by the serum amyloid P component promoter in transgenic mice." J Biochem. 111. 736-738 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami,T.,Yamamura,K.et al.: "Effect of serum amyloid P component level on transtyretin-derived amyloid deposition in a transgenic mouce model of familialamyloidotic polyneuropathy." Am J Pathol. 141. 451-456 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyazaki.,T.,Yamamura,K.et al.: "Prevention of autoimmune insulitis in nonobese dic mice by expression of major histocompatibility complex class ILd molecules." Proc Natl Acad Sci USA. 89. 9519-9523 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Niwa,H.et al.: "Anefficient gene-trap method using poly A trap vectors and characterization of gene trap events." J.Biochem. 113. 343-349 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyori, A.et al: "Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors" J.Biol.Chem. 269. 1323-1331 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toyonaga T.et al: "Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver" Proc.Natl.Acad.Sci.USA. 91. 614-618 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaname, T.et al: "The upstream sequence of a new growth/differebtiation factor, midkine (MK), mediates developmentally regulated lacZ gene expression in transgenic mice" Dvelp.Growth Differ.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 36. 231-238 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama, T.et al: "Exprssion of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice" Gene. 141. 187-192 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mantani, A.et al: "A novel isoform of the neurofibromatosis type-l mRNA and a switch of isoforms during murine cell differentiation and proliferation" Gene. 148. 245-251 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, S.et al: "Improvement of germ line transmission by targeting b-galactosidase to nuclei in transgeic mice" Develop.Growth Differ. 36. 521-527 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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