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1996 Fiscal Year Final Research Report Summary

A New Approach for Physical Functions of Band 3 Based on Molecular Pathobiology of Hereditary Band 3 Deficiency in Cattle

Research Project

Project/Area Number 07456140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

INABA Mutsumi  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00183179)

Co-Investigator(Kenkyū-buntansha) MATSUKI Naoaki  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Inst, 大学院・農学生命科学研究科, 助手 (40251417)
DOI Kunio  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Prof, 大学院・農学生命科学研究科, 教授 (70155612)
ONO Ken-ichiro  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Prof, 大学院・農学生命科学研究科, 教授 (50111480)
Project Period (FY) 1995 – 1996
KeywordsBand 3 / Anion transport / Acid-base homeostasis / Red cell membrane proteins / Hereditary spherocytosis / O_2 / CO_2 transport / Hemolytic anemia / Cattle
Research Abstract

We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE,immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. To elucidate the molecular basis of this aberrant deficiency of the band 3 protein, we cloned red cell band 3 cDNA (-3.5kb) from normal and the affected animal. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C * T substitution resulting in a nonsense mutation (CGA * TGA ; Arg * Stop) at the position of Arg^<664> that corresponded to codon 646 in human red cell band 3 cDNA.The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total dificiency of band 3 also resulted in defective CL^-/HCO_3^- exchange, causing mild acidosis with decreases in the HCO_3^- concentration and total CO_2 in the proband blood. Our results demonstrate that band 3 indeed contributes to red cell membrane stability, CO_2 transport, and acid-base homeostasis, but is not always essential to survival of this mammal.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Koshino,I. et al.: "Molecular basis and genetic diagnosis for hereditary band 3 deficiency in cattle." Biochem.Biophys.Res.Commun.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inaba,M. et al.: "Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation." J.Clin.Invest.97. 1804-1817 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okabe,J. et al.: "Hemoglobin types,erythrocyte membrane skeleton and plasma iron concentration in calves with poikilocytosis." J.Vet.Med.Sci.58. 627-634 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata,Y. et al.: "Complete band 3 deficiency in cattle:A model for hereditary spherocytosis with striking kinstability of cytoskeletal network with marked exo-and endocytosis." Blood. 85. 468- (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsumoto.M. et al.: "Molecular basis of bovine erythroid protein 4.2 polymorphysm." Biochim.Biophys.Acta (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 稲葉 睦: "牛の遺伝性赤血球膜蛋白質異常症" 家畜診療. 401. 73-80 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Horvath, P., et al.: "Multiple elements in the 5'untranslated region down regulate c-sis messenger RNA translation" Cell Growth Differ. 6. 1103-1110 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata, Y., et al.: "Complete band 3 deficiency in cattle : a model for hereditary spherocytosis with striking instability of cytoskeletal network with marked exo- and endocytosis" Blood. 85(Suppl.). 468a (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba, M., et al.: "Defective anion transport and maeked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation" J.Clin.Invest.97. 1804-1817 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okabe, J., et al.: "Hemoglobin types, erythrocyte membrane skeleton and plasma iron concentration in calves with poikilocytosis" J.Vet.Med.Sci.58. 627-634 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koshino, I.: "Molecular basis and genetic diagnosis for hereditary band 3 deficiency in cattle" The University of Tokyo, Bachelor thesis. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto, M.: "Molecular basis of bovine red cell protein 4.2 polymorphism" The University of Tokyo, Bachelor thesis. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koshino, I., et al.: "Molecular basis and genetic diagnosis for hereditary band 3 deficiency in cattle based on cloning of bovine erythroid band 3 cDNA" (Submitted).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto, M.: "Molecular basis of bovine erythroid protein 4.2 polymorphism" (Submitted).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba, M., et al.: "Decreased but non-neglectable expression of band 3 mRNA with Arg^<664>*Stop mutation in homozygotes and heterozygotets of bovine band 3 deficiency" (Manuscript in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inaba, M., et al.: "Remarkably decreased anion fluxes in bovine red cells with hereditary band 3 deficiency" (Manuscript in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneko, N., et al.: "Anion transport with broad substrate specificity and decreased sensitivity to stilbene didslfonate in reticulocytes and its breakdown during cellular maturation" (Manuscript in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuroki, K., et al.: "Molecular analysis of membrane surface area of bovine band 3 by determination of epitopes to several monoclonal antibodies and their genetic analysis" (Manuscript in preparation).

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

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Published: 1999-03-09  

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