• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1998 Fiscal Year Final Research Report Summary

Developmental genetic analysis of mouse dysmyelination mutant, quaking.

Research Project

Project/Area Number 09672311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

ABE Kuniya  KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (40240915)

Project Period (FY) 1997 – 1998
KeywordsMYELIN FORMATION / ATAXIA / OLIGODENDROCYTE / KNOCKOUT MOUSE / BAC / TRANSGENIC MOUSE
Research Abstract

A responsible gene for mouse mutation showing ataxic phenotype was sought and analyzed in order to understand the etiology of the ataxia. [Results] It was found that qkl gene was spanning about 70 kb of genomic region, and consists of at least 10 exons. It gives rise to six distinct transcripts encoding, theoretically, five different protein isoforms. Exons 1 through 4 are shared by all the transcripts, whereas coding exons and two distinct 3'-UTRs downstream to the exon 4 are differentially utilized. One isoform has a truncated KH domain and may act as an antagonist to the others. These mRNA appear to encode a putative RNA binding protein containing one KH motif required for RNA binding activity. We have made three lines of qkl knockout mouse, of which two were analyzed in detail. Mice heterozygous for the KO allele behave normally. However, double heterozygotes in combination with the original qk allele (=qkv) showed rapid tremor, clearly demonstrating that qkl gene is the responsibl … More e gene for the quaking mutation. Furthermore, this double heterozygote compound mice showed even more severe phenotype compared to the qkv/qkv mice ; early onset of convulsion, gait abnormality, or growth retardation. In many ways this phenotype resembles that of some of the human leukodystrophies. This severe phenotype is probably due to premature arrest of myelination : the oligodendrocyte processes fail to properly interact with the axons to form compacted myelin. qkl expression was found to be significantly reduced in qkv homozygotes and was even less in the compound, qkv/qklO.Thus myelination appears to be sensitive to the dosage of qkl. In fact, when qkl level is increased by introduction of BAG clone containing the whole qkl gene, the tremor phenotype was completely recovered. mRNA expression of other myelin genes including PLP, MBP were reduced in the qk mutants, and there were almost no protein products for these genes. Furthermore, mRNA splicing of MAG, PLP and probably MBP is altered by the reduced qkl expression. These results sugegst that qkl is an essential regulator of myelination in CNS, and probably plays important role in post-transcriptional regulation of the myelin genes. Less

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kimura,S.,Abe,K.,Suzuki,M.,Yoshioka,K.,Ogawa,M.,Kaname,T.,Miike,T.and Yamamura,K.: "A 900 bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice." Dev.Growth Diff.39. 257-265 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe,K.and Noce,T.: "A DEAD-box family protein gene,Ddx4,encoding a murine homolog of Drosophila vasa,maps to the distal end of mouse Chromosome 13." Mammalian Genome. 8. 622-623 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka,H.,Abe,K and Kim,C.-H.: "Quaking gene expression in the zebrafish embryo." Mech.Dev.69. 209-213 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaname,T.,Uehara,K.,Abe,K.,Muramatsu,T.and Yamamura,K.: "Testis b-1,4-galactosyltransferase gene maps to mouse chromosome 5." Genomics. 53. 117-118 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuki,Y.,Kaname,T.,Suematsu,S.,Yamaguchi,Y.,Abe,K.and Yamamura,K.: "Mouse K-glypican gene,Gpc4,maps to chromosome X." Genomics. 54. 358-359 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,S.,Fujishita,S.,Ikezawa,M,Ogawa,M.,Abe,K.and Miike,T.: "Muscle type promoter and its first intronabnormalities in dystrophin gene in patients with Duchenne muscular dystrophy." J.Child Neurol.13. 290-292 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe,K.,Ko,M.S.H.and MacGregor,G.R: "A Systematic Molecular Genetic Approach to Study Mammalian Germ Line Development." Int.National J.Dev.Biol.42. 1051-1065 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Kawakami,Mitsunaga,K.,Kikuti,Y.Y.,Ando,A.,Inoko,H.,Yamamura,K.and Abe,K.: "Tctex-3,related to Drosophila Polycomblike,isspecifically expressed in male germ cells andmapped to t-complex of mouse." Mammalian Genome. 9. 874-880 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Vernet,C.Abe,K.and Artzt,K.: "Genetic mapping of 10 microsatellites in the t complex region of mouse chromosome 17" Mammalian Genome. 9. 472 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] ,A.,Kikuti,Y.Y.,Abe,K.,Shigenari,A.,Kawata,H.,Ikemura,T.,Kimura M.,and Inoko,H.: "cDNA cloning,Northern hybridization and mapping Shigenari,A.,Kawata,H.,Ikemura,T.analysis of a putative GDS(guanine nucleotide dissociation,Kimura M.,and Inoko,H.stimulator of G proteins)-related protein gene at the centromeric ends of the human and mouse MHC regions." Immunogenetics. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kondo,T.,Furuta,T.,Mitsunaga,K.,Ebersole,T.,Shichiri,M.,Artzt,K.,Yamamura,K.and K.Abe.: "Genomic organization and expression analysis of the mouse qkI locus." Mammalian Genome. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura, S., Abe, K., Suzuki, M., Yoshioka, K., Ogawa, M., Kaname, T., Miike, T.and Yamamura, K.: "A 900 bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice." Dev.Growth Diff.39. 257-265 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe, K.and Noce, T.: "A DEAD-box family protein gene, Ddx4, encoding a murine homolog of Drosophila vasa, maps to the distal end of mouse Chromosome 13." Mammalian Genome. 8. 622-623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, H., Abe, K and Kim, C.-H.: "Quaking gene expression in the zebrafish embryo." Mech.Dev.69. 209-213 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Kawakami, Mitsunaga, K., Kikuti, Y.Y., Ando, A., Inoko, H., Yamamura, K.and Abe, K.: "Tctex-3, related to Drosophila Polycomblike, is specifically expressed in male germ cells and mapped to t-complex of mouse." Mammalian Genome. 9. 874-880 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaname, T., Uehara, K., Abe, K., Muramatsu, T.and Yamamura, K.: "Testis b-1,4-galactosyltransferase gene maps to mouse chromosome 5." Genomics. 53. 117-118 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuki, Y., Kaname, T., Suematsu, S., Yamaguchi, Y., Abe, K.and Yamamura, K.: "Mouse K-glypican gene, Gpc4, maps to chromosome X." Genomics. 54. 358-359 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, S., Fujishita, S., Ikezawa, M Ogawa, M., Abe, K.and Miike, T.: "Muscle type promoter and its first intron abnormalities in dystrophin gene in patients with Duchenne muscular dystrophy." J.Child Neurol.13. 290-292 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe, K., Ko, M.S.H.and MacGregor, G.R: "A Systematic Molecular Genetic Approach to Study Mammalian Germ Line Development." Int.National J.Dev.Biol.42. 1051-1065 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Vernet, C.Abe, K.and Artzt, K.: "Genetic mapping of 10 microsatellites in the t complex region of mouse chromosome 17" Mammalian Genome. 9. 472 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ando, A., Kikuti, Y.Y., Abe, K., Shigenari, A., Kawata, H., Ikemura, T., Kimura, M., and Inoko, H.: "cDNA cloning, Northern hybridization and mapping analysis of a putative GDS (guanine nucleotide dissociation stimulator of G proteins) -related protein gene at the centromeric ends of the human and mouse MHC regions." Immunogenetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kondo, T., Furuta, T., Mitsunaga, K., Ebersole, T., Shichiri, M., Artzt, K., Yamamura, K.and K.Abe: "Genomic organization and expression analysis of the mouse qkl locus." Mammalian Genome. (in press).

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

URL: 

Published: 1999-12-08  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi