1995 Fiscal Year Annual Research Report

遺伝性赤血球膜異常症の病因・病態の解明に関する遺伝細胞生化学的、分子電顕的研究

Research Project

Project/Area Number	07457236
Research Category	Grant-in-Aid for General Scientific Research (B)
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)	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 / 遺伝性球状赤血球症 / band 4.2 / band 3 / 形態形成 / β-spectrin / 遺伝子解析 / 免疫電顕
Research Abstract	遺伝性赤血球膜異常症の病因および病態に関するわが国の特質を明らかにすることを目的として研究を遂行した。 (1)わが国で、最も高頻度である遺伝性球状赤血球症(HS)のphenotype病態の解析:その結果、がわ国のHSでは、諸外国で最も頻度の高いとされているankyrinおよびspectrinの異常症は低頻度であり、むしろband 3およびband 4.2異常症が主体であることが判明した。現在、genotypeの面から、本邦HS症例の特徴について鋭意解析を進めている。 (2)わが国特有と考えられている多様なband 4.2異常症の遺伝子解析および病態分析と、band 4.2蛋白の構造と機能解析:その結果、既に判明しているNippon Typeのband 4.2欠損症に加えて、band 4.2 Komatsu (523 GAT→TAT ; homozygote)、band 4.2 Shiga (317 CGC→TGC/142 GCT→ACT ; compound heterozygote)を同定・公表した。さらに、band 4.2の生理的機能に関して、これらのband 4.2欠損症の電顕学的、物性学的手法による病態研究を通じて、band 4.2が細胞骨格蛋白(特にspectrin)に結合する可能性が高いという新事実を明らかにした。 (3)構造蛋白band 3の正常と病態の研究:完全band 3欠損症(ウシ赤血球)を世界第一例として発見・同定した。本例では著しい細胞膜の不安定性、全身acidosisを生じ、band 3の生理的意義を明らかにしえた。 (4)赤芽球前駆細胞を用いた赤血球系各膜蛋白に関するmRNAの発現およびこれに伴う蛋白発現による赤血球膜の全体としての形態形成(morphogenesis)の研究:主として蛋白化学および遺伝子学的手法を用いて、赤芽球においては、まずspectrin、band 3の発現が、次いでankyrin、band 4.1が、そしてband 4.2の発現は赤芽球分化の最終段階に至って初めて認められることを明らかにした。

Research Products
(12 results)

All Other

All Publications (12 results)

[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." International Journal of Hematology. 61. 165-178 (1995)
[Publications] Kanzaki, A.: "Band 4.2 Siga : 317 CGC→TGC in compound heterozygetes with 142 CGT→ACT results in band 4.2 deficiency and microspherocytosis." British Journal of Haematology. 91. 333-340 (1995)
[Publications] Marechal, J.: "Ethnic distribution of allele α^<LELY>, a low expression allele of red cell spectrin α-gene." British Journal of Haematology. 90. 553-556 (1995)
[Publications] Okamoto, N.: "Hereditary spherocytic anemia with deletion of the short arm of chromosome 8." American Journal of Medical Genetics. 58. 225-229 (1995)
[Publications] Yawata, Y.: "Complete band 3 deficiency in cattle : A model for hereditary spherocytosis with striking instability of cytoskeletal network with marked exo-and endocytosis." Blood. 86. 468a (1995)
[Publications] Kanzaki, A.: "The definitive role of band 4.2 in completing whole assembly of red cell membrane structure by the latest expression with five isoforms among membrane proteins at the terminal erythroid maturation." Blood. 86. 469a (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 Motility and the Cytoskeleton. 33. 95-105 (1996)
[Publications] Maillet, P.: "A stop codon in exon 30 of β-spectrin gene associated with hereditary elliptocytosis in spectrin Nagoya." Human Mutation. (in press). (1996)
[Publications] Golan, D. E.: "Control of band3 lateral and rotational mobility by band 4.2 in intact erythrocytes : Release of band 3 oligomers from low-affinity binding sites." Biophysical Journal. (in press). (1996)
[Publications] Inaba, M.: "Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 due to a nonsense mutation." Journal of Clinical Investigation. (in press). (1996)
[Publications] Yawata, Y.: "Novel evidence of binding of red cell membrane protein band 4.2 to spectrins critical for the final membrane assembly and membrane stability." Proceedings of the International Symposium on Membrane Proteins : Structure, Function and Expression Control (Fukuoka). 87 (1996)
[Publications] Kanzaki, A.: "The completion of whole assembly of red cell membrane structure by the latest expression of band 4.2 with five isoforms among membrane proteins at the terminal erythroid maturation." Proceeding of the International Symposium on Membrane Proteins : Structure, Function and Expression Control (Fukuoka). 88 (1996)

1995 Fiscal Year Annual Research Report

遺伝性赤血球膜異常症の病因・病態の解明に関する遺伝細胞生化学的、分子電顕的研究

Principal Investigator

八幡 義人 川崎医科大学, 医学部, 教授 (70069011)

Research Products

[Publications] Kanzaki, A.: "Band 4.2 Siga : 317 CGC→TGC in compound heterozygetes with 142 CGT→ACT results in band 4.2 deficiency and microspherocytosis." British Journal of Haematology. 91. 333-340 (1995)

[Publications] Marechal, J.: "Ethnic distribution of allele α^<LELY>, a low expression allele of red cell spectrin α-gene." British Journal of Haematology. 90. 553-556 (1995)

[Publications] Okamoto, N.: "Hereditary spherocytic anemia with deletion of the short arm of chromosome 8." American Journal of Medical Genetics. 58. 225-229 (1995)

[Publications] Yawata, Y.: "Complete band 3 deficiency in cattle : A model for hereditary spherocytosis with striking instability of cytoskeletal network with marked exo-and endocytosis." Blood. 86. 468a (1995)

[Publications] Kanzaki, A.: "The definitive role of band 4.2 in completing whole assembly of red cell membrane structure by the latest expression with five isoforms among membrane proteins at the terminal erythroid maturation." Blood. 86. 469a (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 Motility and the Cytoskeleton. 33. 95-105 (1996)

[Publications] Maillet, P.: "A stop codon in exon 30 of β-spectrin gene associated with hereditary elliptocytosis in spectrin Nagoya." Human Mutation. (in press). (1996)

[Publications] Golan, D. E.: "Control of band3 lateral and rotational mobility by band 4.2 in intact erythrocytes : Release of band 3 oligomers from low-affinity binding sites." Biophysical Journal. (in press). (1996)

[Publications] Inaba, M.: "Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 due to a nonsense mutation." Journal of Clinical Investigation. (in press). (1996)

八幡義人川崎医科大学, 医学部, 教授 (70069011)