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Study on recombination signal binding protein ; RBP-Jkappa

Research Project

Project/Area Number 04044094
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKyoto University, Faculty of Medicine

Principal Investigator

NAKANO Toru  Kyoto University, Faculty of Medicine, Lectureer, 医学部, 講師 (00172370)

Co-Investigator(Kenkyū-buntansha) TSUBATA Takeshi  Kyoto University, Faculty of Medicine, 医学部, 助教授 (80197756)
ASHBURNER Michael  Cambridge University
MAK Tak W.  Ontario Cancer Institute, Toronto University
清水 章  京都大学, 遺伝子実験施設, 教授 (00162694)
川市 正史  京都大学, 医学部, 助教授 (00195041)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1993: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1992: ¥4,100,000 (Direct Cost: ¥4,100,000)
KeywordsGene targeting / Homologous recombination / Embryonic lethal / Development / Transcriptional regulator / 胚性幹細胞 / ショウジョウバエ / 末梢神経 / 遺伝子組換え
Research Abstract

The Jkappa-RBP gene was cloned as the gene which encodes the protein binding to the immunoglobulin recombination signal sequence flanking the kappa-type J segment (Jkappa-RS). However, expression of the gene is not restricted to the lymphoid system. And no functions of mouse Jkappa-RBP other than binding to Jkappa-RS have been found. Meanwhile, the Drosophila homologue of Jkappa-RBP gene turned out to be the gene known as Suppressor of Hairless (Sup(H)) whose mutation affects peripheral nervous system development, suggesting that the Jkappa-RBP gene is also involved in mouse neural development.
To elucidate the functions of Jkappa-RBP gene in mice, we have used homologous recombination in embryonic stem (ES) cells to derive null alleles of the gene. Mouse chimeras produced from two ES clones transmitted the mutated allele to their offspring. Mice with one disrupted Jkappa-RBP allele did not show any overt abnormalities. Heterozygotes for the mutation in the Jkappa-RBP gene were intercrossed to assess the effect of the loss of Jkappa-RBP in homozygous offspring. None of the new born and adult mice were homozygotes suggesting homozygous lethality at embryonic stage. Genotype analysis of embryos shows that homozygous embryos die between day 8.5 and 10.5 of gestation. Homozygous embryos of day 9.5 show 1) anterior opening of neural tube, 2) incomplete turning, and 3) microencephaly.

Report

(2 results)
  • 1993 Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Tashiro,K.,Tada,H.,Heilker,R.,Shirozu,M.,Nakano,T.and Honjo,T.: "Signal sequence trap: a cloning strategy for secreted protein and type I transmembrane proteins" Science. 261. 600-603 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Aoki,T.,Tashiro,K.,Miyatake,S.,Kinashi,T.,Nakano,T.,Oda,Y.,Kikuchi,H.and Honjo,T.: "Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo" Proc.Natl.Acad.Sci.U.S.A.89. 3850-3854 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tashiro,K., Tada,H., Heilker,R., Shirozu,M., Nakano,T. and Honjo,T.: "Signal sequence trap : a cloning strategy for secreted protein and type I transmembrane proteins" Science. 261. 600-603 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Aoki,T., Tashiro,K., Miyatake,S., Kinashi,T., Nakano,T., Oda,Y., Kikuchi,H. and Honjo,T.: "Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo." Proc. Natl. Acad. Sci. U.S.A.89. 3850-3854 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.NAKANO,T.Graf: "Identification of genesdifferentially expressed in two types of v-myb-transformed avian myelomonocytic cells." Oncogene. 7. 527-534 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.FURUKAWA,S.MARUYAMA,M.KAWAICHI,T.HONJO: "The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development." Cell. 69. 1191-1197 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.KAWAICHI,C.OKA,S.SHIBAYAMA,A.E.Koromilas,N,MATSUNAMI,Y.HAMAGUCHI,T.HONJO: "Genomic organization of mouse J_k recombination signal binding protein (RBP-J_k)gene." J.Biol.Chem.267. 4016-4022 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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