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1999 Fiscal Year Final Research Report Summary

A control mechanism of gene expression in red cell membranes

Research Project

Project/Area Number 10044329
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKAWASAKI MEDICAL SCHOOL

Principal Investigator

YAWATA Yoshihito  Medicine, Kawasaki Medical School, Professor, 医学部, 教授 (70069011)

Co-Investigator(Kenkyū-buntansha) KANZAKI Akio  Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (40148698)
SUGIHARA Takashi  Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (60140505)
YAMADA Osamu  Medicine, Kawasaki Medical School, Associate Professor, 医学部, 助教授 (50104790)
WADA Hideho  Medicine, Kawasaki Medical School, Assistant Professor, 医学部, 講師 (70191830)
Project Period (FY) 1998 – 1999
KeywordsRed cell membrane / Gene expression / Hereditary spherocytosis / molecular electron microscopy / Spectrin / Band 3 / Ankyrin / Gene methylation
Research Abstract

(I) Characterization of the phenotypes of red cell membrane disorders :
During our research term for 2 years (1998 and 1999), we have studied 175 cases from 135 kindred of congenital red cell membrane disorders including 118 patients from 100 kindred of hereditary spherocytosis (HS). Clinical phenotypes were determined by clinical hematology studies, membrane protein biochemistry, molecular electron microscopy, and biophysical analyses.
(II) Genotypic analyses in HS :
On the band 3 gene (EPB3), 12 pathognomonic mutations were detected : 4 frameshift mutations and 8 missense mutations with 7 gene polymorphisms. On the ankyrin gene (ANK1), 16 pathognomonic mutations (4 nonsense mutations, 8 frameshift mutations, and 4 abnormal splicings) with 17 gene polymorphisms (2 missense mutations and 15 silent mutations) were identified. On the protein 4.2 gene (ELB42), 3 pathognomonic missense mutations had been found.
(III) Sequential expression of membrane proteins during erythroid differentiation :
In human red cell membranes, spectrins and band 3 were expressed in early erythroid precursors, protein 4.1 followed, and protein 4.2 was finally expressed at the very late erythroblasts sequentially.
(IV) The state of methylation of 5'-CpG-3' sites of the promoter regions of EPB3, SPTB, and ELB42
In SPTB, all of the 5'-CpG-3' sites were totally unmethylated, in contrast to nearly total methylation in EPB3. In ELB42, methylation was absent in very early erythroblasts, although all the sites were nearly completely methylated in mature erythroid cells.

  • Research Products

    (61 results)

All Other

All Publications (61 results)

  • [Publications] Inoue T: "Homozygous missense mutation (band 3 Fukuoka : G130R) : A mild form of hereditary spherocytosis with nearly normal band 3 content, and minimal changes of membrane ultrastructure despite moderate deficiency of protein 4.2"Brit.J.Haematol.. 102. 932-939 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Hereditary stomatocytosis and protein 4.2 abnormalities"Molecular Medical Genetics. 37 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Phenotypic expression in hereditary spherocytosis aggravated by combined band 3 mutations (G714R, K56E & P854L/G130R)"Brit.J.Haematol.. 102. 303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Lack of site-specific methylation patterns of the genomic DNA of red cell membrane band 3 gene in three independent families with total deficiency of protein 4.2 (the Nippon type, P4.2 Komatsu and P4.2 Shiga)"Blood. 92・Suppl 1. 10b (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata A: "Pathogenesis of the disrupted cytoskeletal network in hereditary spherocytosis with ankyrin Marburg : Abnormal conformation of ankyrin molecules associated with decreased amount of spectrins and ankyrins"Blood. 92・Suppl 1. 10b (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "本邦における溶血性貧血"日本医師会雑誌. 120. 37-42 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "赤血球膜異常症の研究史とわが国の特色"細胞. 30・6. 256-258 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神崎暁郎: "赤血球膜骨格蛋白とその異常"細胞. 30・6. 259-263 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡愛弓: "分子電顕から見た膜異常"細胞. 30・6. 277-280 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 賀来万由美: "赤血球膜異常症の分子病態"臨床医. 24. 1017-1019 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "溶血性貧血"医学と薬学. 40. 25-31 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada H: "Late expression of red cell membrane protein 4.2 in normal human erythroid maturation with seven isoforms of the protein 4.2 gene"Exp.Hematol.. 27. 54-62 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Hemolytic disorders in Japan : Diagnosis and Therapy"Asian Med.J.. 42・3. 137-146 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "The 5′-CpG-3′ sites on the promoter region of red cell membrane protein genes (SPTB,EPB3, and ELB42) are methylation-sensitive, and may contribute to erythroid differentiation"Blood. 94・Suppl 1. 188a (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashima H: "Germline mosaicism of MPZ Gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis"Neuromuscul Disord. 9. 232-238 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "わが国の遺伝性球状赤血球症の特徴"日本内科学会雑誌. 88・増刊. 94 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神崎暁郎: "遺伝性球状赤血球症における膜蛋白欠損と遺伝子解析"日本内科学会雑誌. 88・6. 1003-1009 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "わが国の遺伝性球状赤血球症の特徴"日本内科学会雑誌. 88・9. 1825-1833 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "赤血球膜異常症の解明-その黎明から光輝まで-(I)"臨床血液. 40. 1133-1143 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "赤血球膜異常症の解明-その黎明から光輝まで-(II)"臨床血液. 40. 1223-1235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Characteristic features of genotype and phenotype of hereditary spherocytosis in the Japanese population"Int.J.Hematol.. 71・2. 118-135 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells"Gene Function and Disease. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Remus R: "The dynamic state of DNA methylation in the promoter regions of the human band 3, protein 4.2 and β-spectrin genes"Blood. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Atlas de Doencas Hematologicas"Martin Dunitz Ltd. 211 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "赤血球"医学書院. 25 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "専門医のための血液学レビュー '98-'99"総合医学社. 9 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "医学のあゆみState of Arts 2."医歯薬出版. 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "医学のあゆみState of Arts 2."医歯薬出版. 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "血液症候群 I"日本臨牀社. 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "血液症候群 I"日本臨牀社. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神崎暁郎: "血液症候群 I"日本臨牀社. 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神崎暁郎: "血液症候群 I"日本臨牀社. 7 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田治: "血液症候群 I"日本臨牀社. 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 和田秀穂: "血液症候群 I"日本臨牀社. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 和田秀穂: "血液症候群 I"日本臨牀社. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 賀来万由美: "血液症候群 I"日本臨牀社. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神崎暁郎: "血液症候群 I"日本臨牀社. 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田治: "血液症候群 I"日本臨牀社. 3 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "血液症候群 III"日本臨牀社. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "Medical Practice:貧血と多血"文光堂. 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "Molecular Medicine:症候・病態の分子メカニズム"中山書店. 3 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 賀来万由美: "疾患別最新処方(改訂第3版)"Medical View社. 2 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "大学病院における診断と治療:貧血・出血傾向・白血病"真興交易医書出版. 8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "Annual Review血液1999"中外医学社. 10 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "内科学"文光堂. 4 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "内科学 第7版"朝倉書店. 13 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "今日の治療指針"医学書院. 2 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八幡義人: "外来診療のすべて"Medical View社. 2 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yawata Y: "Conn's Current Therapy"W.B.Saunders. 4 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue T, et al: "Homozygous missense mutation (band 3 Fukuoka : G130R) : A mild form of hereditary spherocytosis with nearly normal band 3 content, and minimal changes of membrane ultrastructure despite moderate deficiency of protein 4.2"Brit.J.Haematol.. 102. 932-939 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Hereditary stomatocytosis and protein 4.2 abnormalities"Molecular Medical Genetics. 37 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Phenotypic expression in hereditary spherocytosis aggravated by combined band 3 mutations (G714R, K56E & P854L/G130R)"Brit.J.Haematol.. 102. 303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Lack of site-specific methylation patterns of the genomic DNA of red cell membrane band 3 gene in three independent families with total deficiency of protein 4.2 (the Nippon type, P4.2 Komatsu and P4.2 Shiga)"Blood. 92(Suppl.1). 10b (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata A, et al: "Pathogenesis of the disrupted cytoskeletal network in hereditary spherocytosis with ankyrin Marburg : Abnormal conformation of ankyrin molecules associated with decreased amount of spectrins and ankyrins"Blood. 92(Suppl.1). 10b (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada H, et al: "Late expression of red cell membrane protein 4.2 in normal human erythroid maturation with seven isoforms of the protein 4.2 gene"Exp.Hematol.. 27. 54-62 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Hemolytic disorders in Japan : Diagnosis and Therapy"Asian Med.J.. 42(3). 137-146 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "The 5'-CpG-3 sites on the promoter region of red cell membrane-protein genes (SPTB, EPB3, and ELB42) are methylation-sensitive, and may contribute to erythroid differentiation"Blood. 94(Suppl.1). 188a (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takashima H, et al: "Germline mosaicism of MPZ Gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis"Neuromuscul Disord. 9. 232-238 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Characteristic features of genotype and phenotype of hereditary spherocytosis in the Japanese population"Int.J.Hematol.. 71. 118-135 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yawata Y, et al: "Genotypic and phenotypic expressions of protein 4.2 in human erythroid cells"Gene Function and Disease. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Remus R, et al: "The dynamic state of DNA methylation in the promoter regions of the human band 3, protein 4.2 and β-spectrin genes"Blood. (in press). (2000)

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

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Published: 2001-10-23  

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