1994 Fiscal Year Annual Research Report

遺伝性赤血球膜異常症の病因・病態に関する生化学的・分子遺伝学的研究

Research Project

Project/Area Number	06044212
Research Institution	Kawasaki Medical School
Principal Investigator	八幡義人川崎医科大学, 医学部, 教授 (70069011)
Co-Investigator(Kenkyū-buntansha)	DELAUNAY Jea Institut Pasteur de Lyon, CNRS(URA 1171), 教授 ALLOISIO Nic Institut Pasteur de Lyon, CNRS(URA 1171), Senior Sci 原野恵子川崎医療福祉大学, 医療技術学部, 講師 (00069072) MORLE Lauret Institut Pasteur de Lyon, CNRS(URA 1171), Senior Sci 原野昭雄川崎医科大学, 医学部, 助教授 (60069028) 高橋美加川崎医科大学, 医学部, 助手 (10258212) 岡本直人川崎医科大学, 医学部, 助手 (20204042) 井上孝文川崎医科大学, 医学部, 助手 (60203238) 和田秀穂川崎医科大学, 医学部, 講師 (70191830) 神崎暁郎川崎医科大学, 医学部, 講師 (40148698) 杉原尚川崎医科大学, 医学部, 講師 (60140505) 山田治川崎医科大学, 医学部, 助教授 (50104790)
Keywords	赤血球膜 / 遺伝子解析 / 溶血性貧血 / 遺伝性球状赤血球症 / 形態形成 / 細胞骨格蛋白 / 構造蛋白 / 免疫電顕
Research Abstract	(1)わが国における赤血球膜異常症症例の集積とその疫学的特性の解明: 赤血球膜異常症自験610症例を検索し、わが国におけるその疫学的特徴を明らかにしえた。その結果、遺伝性球状赤血球症(HS)が最も高頻度であり、ついで遺伝性楕円赤血球症(HE)、遺伝性有口赤血球症(HSt)となり、これらの主体は赤血球膜蛋白異常症であり、膜脂質異常症は数%と判明した。この膜蛋白異常症のうち、わが国のHSでは、欧米(spectrin・ankyrin異常が主要因)とは異なり、band 3・band 4.2異常症が主体であることを明らかにした。また本年度の研究対象として特にband 4.2異常症とspectrin異常症を取りあげた。 (2)Band 4.2異常症: Band 4.2欠損症自験34症例を同定し、わが国においてはband 4.2遺伝子の異常として、(a)codon 142Ala→Thr点変異症例(Nippon type)が主体であることが判明した。さらに、(b)2種の新しいband 4.2異常症、すなわち(i)band 4.2 Komatsu(175GAT→TAT)と(ii)band 4.2 Shiga(317CGC→TGC/142GCT→ACT)を同定した。(c)band4.2完全欠損症を示すband 3 Okinawaについて共同研究を継続中である。次いで(d)赤芽球の分化過程における膜蛋白、特にband 4.2の遺伝子発現と蛋白表出を明らかにした。 (3)Spectrin異常症: (a)β-Spectrin異常症についてSpectrin Le Puy in Yamagata(β^<220/214>)の遺伝子異常を同定し、その赤血球膜細胞骨格形成障害を免疫電顕的に明らかにした。さらに新たに(b)β-Spectrin Nagoya(β^<220/217>)の遺伝子異常をも同定した。(c)α-spectrinについては、allele α^<LELY>について日本人における頻度を明らかにした。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Yawata,Y.: "Invited review: Red cell membrane protein band 4.2: Phenotypic,genetic,and electron microscopic aspects." Biochim.Biophys.Acta: Protein Structure and Molecular Enzymology Reviews. 1204. 131-148 (1994)
[Publications] Yawata,Y.: "Invited review: Band 4.2 abnormalities in human red cells." Am.J.Med.Sci.307. 190-203 (1994)
[Publications] Yawata,A.: "A surface replica method:A useful tool for studies of the cytoskeletal network in red cell membranes of normal subjects and patients with a β-spectrin mutant (spectrin Le Puy: β220/214)." Virchows Arch.425. 297-304 (1994)
[Publications] Marechal,J.: "Hereditary elliptocytosis associated with spectrin Le Puy in a Japanese family: Ultrastructural aspect of the red cell skeleton." Eur.J.Haematol.52. 92-98 (1994)
[Publications] Inoue,T.: "Electron microscopic and physicobiochemical studies on disorganization of cytoskeletal network and integral protein (band 3)in red cells of band 4.2 deficiency with a mutation (codon 142 GCT→ACT)." Int.J.Hematol.59. 157-175 (1994)
[Publications] Yawata,Y.: "Red cell membrane disorders in the Japanese population: Clinical,biochemical,electron microscopic,and genetic studies." Int.J.Hematol.60. 23-38 (1994)
[Publications] Inoue,T.: "Uniquely higher incidence of isolated or combined deficiency of band 3 and/or band 4.2 as the pathogenesis of autosomal dominantly inherited hereditary spherocytosis in the Japanese population." Int.J.Hematol.60. 227-238 (1994)
[Publications] Sugihara,T.: "Deformation of swollen erythrocytes provides a model of sickling induced leak pathways,including a novel bromide sensitive component." Blood. 83. 2684-2691 (1994)
[Publications] Yawata,Y.: "Expression of band 4.2 and its isoforms in human erythroid precursors." Blood. 84. 5a- (1994)
[Publications] Yawata,Y.: "Two novel mutations in red cell band 4.2 deficiency: Homozygous 175 GAT→TAT,and compound heterozygous 142 GCT→ACT with 317 CGC→TGC." Blood. 84. 7a- (1994)
[Publications] Yawata,Y.: "Abnormalities of red cell band 4.2 on its anchoring functions." Pathophysiol.1(Suppl). 235- (1994)
[Publications] Kanzaki,A.: "Band 4.2 Komatsu: 523 GAT→TAT(175 Asp→Tyr)in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2,hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network." Int.J.Hematol.(in press). (1995)
[Publications] Marechal,J.: "Ethnic distribution of allele α^<LELY>,a low expression allele red cell spectrin α-gene." Br.J.Haematol.(in press). (1995)
[Publications] Maillet,P.: "A stop codon in exon X of β-spectrin gene associated with hereditary elliptocytosis in spectrin Nagoya." Hum.Mutat.(in press). (1995)
[Publications] Yawata,A.: "Complete band 3 deficiency in bovine red cells. II. Marked spherocytosis with budding formation due to striking instability of cytoskeletal network." J.Clin.Invest.(submitted). (1995)
[Publications] Yawata,Y.: "Electron microscopic evidence of impaired intramembrane particles and of instability of cytoskeletal network in band 4.2 deficiency in human red cells." Cell Motil.Cytoskeleton. (submitted). (1995)
[Publications] Kanzaki,A.: "Band 4.2 Shiga: A novel compound heterozygous mutation of 317 CGC→TGC with 142 GCT→ACT in red cell band 4.2deficiencywithmicrospherocytosis." Br.J.Haematol.(submitted). (1995)
[Publications] 八幡義人: "遺伝子診断と遺伝子治療(村松正実、平井久丸編)" 東京化学同人(東京), 7 (1994)
[Publications] 八幡義人: "血液病学第2版(三輪史郎、柴田昭、青木延雄編)" 文光堂(東京), 38 (1995)
[Publications] 神崎暁郎: "Annual Review血液1995" 中央医学社(東京), 19 (1995)
[Publications] 八幡義人: "遺伝子診断実践ガイド(中井利昭他編)" 中央医学社(東京), 10 (1995)

1994 Fiscal Year Annual Research Report

遺伝性赤血球膜異常症の病因・病態に関する生化学的・分子遺伝学的研究

Principal Investigator

八幡 義人 川崎医科大学, 医学部, 教授 (70069011)

Research Products

[Publications] Yawata,Y.: "Invited review: Red cell membrane protein band 4.2: Phenotypic,genetic,and electron microscopic aspects." Biochim.Biophys.Acta: Protein Structure and Molecular Enzymology Reviews. 1204. 131-148 (1994)

[Publications] Yawata,Y.: "Invited review: Band 4.2 abnormalities in human red cells." Am.J.Med.Sci.307. 190-203 (1994)

[Publications] Yawata,A.: "A surface replica method:A useful tool for studies of the cytoskeletal network in red cell membranes of normal subjects and patients with a β-spectrin mutant (spectrin Le Puy: β220/214)." Virchows Arch.425. 297-304 (1994)

[Publications] Marechal,J.: "Hereditary elliptocytosis associated with spectrin Le Puy in a Japanese family: Ultrastructural aspect of the red cell skeleton." Eur.J.Haematol.52. 92-98 (1994)

[Publications] Inoue,T.: "Electron microscopic and physicobiochemical studies on disorganization of cytoskeletal network and integral protein (band 3)in red cells of band 4.2 deficiency with a mutation (codon 142 GCT→ACT)." Int.J.Hematol.59. 157-175 (1994)

[Publications] Yawata,Y.: "Red cell membrane disorders in the Japanese population: Clinical,biochemical,electron microscopic,and genetic studies." Int.J.Hematol.60. 23-38 (1994)

[Publications] Inoue,T.: "Uniquely higher incidence of isolated or combined deficiency of band 3 and/or band 4.2 as the pathogenesis of autosomal dominantly inherited hereditary spherocytosis in the Japanese population." Int.J.Hematol.60. 227-238 (1994)

[Publications] Sugihara,T.: "Deformation of swollen erythrocytes provides a model of sickling induced leak pathways,including a novel bromide sensitive component." Blood. 83. 2684-2691 (1994)

[Publications] Yawata,Y.: "Expression of band 4.2 and its isoforms in human erythroid precursors." Blood. 84. 5a- (1994)

[Publications] Yawata,Y.: "Two novel mutations in red cell band 4.2 deficiency: Homozygous 175 GAT→TAT,and compound heterozygous 142 GCT→ACT with 317 CGC→TGC." Blood. 84. 7a- (1994)

[Publications] Yawata,Y.: "Abnormalities of red cell band 4.2 on its anchoring functions." Pathophysiol.1(Suppl). 235- (1994)

[Publications] Kanzaki,A.: "Band 4.2 Komatsu: 523 GAT→TAT(175 Asp→Tyr)in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2,hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network." Int.J.Hematol.(in press). (1995)

[Publications] Marechal,J.: "Ethnic distribution of allele α^<LELY>,a low expression allele red cell spectrin α-gene." Br.J.Haematol.(in press). (1995)

[Publications] Maillet,P.: "A stop codon in exon X of β-spectrin gene associated with hereditary elliptocytosis in spectrin Nagoya." Hum.Mutat.(in press). (1995)

[Publications] Yawata,A.: "Complete band 3 deficiency in bovine red cells. II. Marked spherocytosis with budding formation due to striking instability of cytoskeletal network." J.Clin.Invest.(submitted). (1995)

[Publications] Yawata,Y.: "Electron microscopic evidence of impaired intramembrane particles and of instability of cytoskeletal network in band 4.2 deficiency in human red cells." Cell Motil.Cytoskeleton. (submitted). (1995)

[Publications] Kanzaki,A.: "Band 4.2 Shiga: A novel compound heterozygous mutation of 317 CGC→TGC with 142 GCT→ACT in red cell band 4.2deficiencywithmicrospherocytosis." Br.J.Haematol.(submitted). (1995)

[Publications] 八幡義人: "遺伝子診断と遺伝子治療(村松正実、平井久丸 編)" 東京化学同人(東京), 7 (1994)

[Publications] 八幡義人: "血液病学 第2版(三輪史郎、柴田昭、青木延雄 編)" 文光堂(東京), 38 (1995)

[Publications] 神崎暁郎: "Annual Review血液1995" 中央医学社(東京), 19 (1995)

[Publications] 八幡義人: "遺伝子診断実践ガイド(中井利昭 他編)" 中央医学社(東京), 10 (1995)

八幡義人川崎医科大学, 医学部, 教授 (70069011)

[Publications] 八幡義人: "遺伝子診断と遺伝子治療(村松正実、平井久丸編)" 東京化学同人(東京), 7 (1994)

[Publications] 八幡義人: "血液病学第2版(三輪史郎、柴田昭、青木延雄編)" 文光堂(東京), 38 (1995)

[Publications] 八幡義人: "遺伝子診断実践ガイド(中井利昭他編)" 中央医学社(東京), 10 (1995)