1999 Fiscal Year Final Research Report Summary
Molecular and Biochemical Studies on Compensatory Mechanisms for Total Band 3 Deficiency in Japanese Black Cattle
| Project/Area Number |
09460145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
INABA Mutsumi Graduate School of Agricultural and Life Sciences, The University of Tokyo, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00183179)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUKI Naoaki Graduate School of Agricultural and Life Sciences, The University of Tokyo, Assistant Professor, 大学院・農学生命科学研究科, 助手 (40251417)
DOI Kunio Graduate School of Agricultural and Life Sciences, The University of Tokyo, Professor, 大学院・農学生命科学研究科, 教授 (70155612)
TAKAHASHI Michio Ajinomoto Co., Inc., Corporate Advisor, 顧問(研究職) (30011943)
TAKAKUWA Yuichi Medical School, Tokyo Women's Medical University, Professor, 医学部, 教授 (40113740)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Red cells / Membrane proteins / Band 3 / Hereditary diseases / Anion transport / Acid-base balance / Membrane skeleton / Japanese black cattle |
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| Research Abstract |
Band 3 has been believed to be essential to survival of mammals. The aim of this research project is to define compensatory mechanisms for total band 3 deficiency in cattle.
1) Linkage analyses showed that the genotype for R664X mutation determined by PCR-RFLP coinherited with the red cell phenotype of dominantly inherited HS and band 3 deficiency, demonstrating that R664X mutation is the principal molecular cause for dominant hereditary band 3 deficiency in cattle associated with HS.
2) Extensive studies on the red cell membrane proteins demonstrated that the major proximal causes for the membrane instability of homozygous and heterozygous cells appear to be the loss of band 3-ankyrin-spectrin association, and the reduction of spectrin, respectively. Quantitation of mutant mRNA co-injection of normal and mutant RNA into Xenopus oocytes, and in vitro synthesis/immunoprecipitation of normal and the mutant bend 3 demonstrated a dominant-negative effect of the mutant protein in vivo on the expression of normal band 3. A hypothetical possibility for pathogenesis of HS in the affected animals involves : (1) Band 3-independent assembly of membrane skeleton to the plasma membrane. (2) Translocation of reduced normal band 3-ankyrin and their association with spectrin to strengthen interactions between the lipid bilayer and the skeleton in heterozygous but not m homozygous red cells.
3) Bovine red cells with total band 3 deficiency possessed anion transport activity mediated by AE2, with substrate specificity an sensitivity to stilbene disulfonate which were extremely lower than those in normal cells. T e rapid anion exchange was not compensated at all, indicating that the function of band 3 is not obligatory to 0ィイD22ィエD2/C0ィイD22ィエD2 exchange.
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Research Products
(23 results)
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[Publications] Nunomura, W., Takakuwa, Y., Tokimitsu, R., Krauss, S. W., Kawashima, M., and Mohandas, N.: "Regulation of CD44-protein 4.1 interaction by CaィイD12+ィエD1 and calmodulin. Implications for modulation of CD44 ankyrin interaction."J. Biol. Chem.. 272. 30332-30328 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Thongsong, B., Mukai, K., Bonkobara, M., Matsuki, N., Inaba, M., and Ono, K.: "Proline uptake by equine placental microvillous membrane vesicles."J. Equine Sci.. 10. 21-25 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Uchide, T., Onda, K., Bonkobara, M., Matsuki, N., Inaba, M., and Ono, K.: "Utilization of intestinal triglyceride-rich lipoprotein (TRL) in mammary gland in cows."J. Vet. Med. Sci.. 61. 1143-1146 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Sato, K., Inaba, M., Suwa, Y., Matsuu, A., Hikasa, Y., Ono, K., and Kagota, K.: "Inherited defects of Na-dependent glutamate transport mediated by glutamate/aspartate transporter in canine red cells due to a decreased level of transporter protein expression."J. Biol. Chem.. 275. 6620-6627 (2000)
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[Publications] Kuroki, K., Inaba, M., Matsumoto, M., Ono, K., and Amano, T.: "Molecular analysis of membrane surface area of bovine and 3 by determination of epitopes to several monoclonal antibodies and their genetic analysis, (in preparation)"(in preparation).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Inaba, M.: "(2000) Chapter 156 : Red blood cell membrane defects. In Schalm's Veterinary Hematology, 5th ed.(Feldman, R. F. Zinkl, J. G., and Jain, N. C. eds.) Lippincott Williams and Wilkins, New York, 2OOO. Schalm's Veterinary Hematology, 5th ed. (Feldman, R. F. Zinkl, J. G., and Jain, N. C. eds.) (in press)"Lippincott Williams and Wilkins, New York. (2000)
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「研究成果報告書概要(欧文)」より
