Grant-in-Aid for Scientific Research (B)
|Research Institution||KAWASAKI MEDICAL SCHOOL|
YAWATA Yoshihito Kawasaki Medical School, Medicine, Professor, 医学部, 教授 (70069011)
岡本 直人 川崎医科大学, 医学部, 助手 (20204042)
INOUE Takafumi Kawasaki Medical School, Medicine, Research Associate, 医学部, 助手 (60203238)
WADA Hideho Kawasaki Medical School, Medicine, Assistant Professor, 医学部, 講師 (70191830)
KANZAKI Akio Kawasaki Medical School, Medicine, Assistant Professor, 医学部, 講師 (40148698)
SUGIHARA Takashi Kawasaki Medical School, Medicine, Assistant Professor, 医学部, 講師 (60140505)
YAMADA Osamu Kawasaki Medical School, Medicine, Associate Professor, 医学部, 助教授 (50104790)
|Project Fiscal Year
1995 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥7,300,000 (Direct Cost : ¥7,300,000)
Fiscal Year 1996 : ¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1995 : ¥4,800,000 (Direct Cost : ¥4,800,000)
|Keywords||Red cell membrane / Gene analysis / Hereditary spherocytosis / Spectrin / Band 3 / Protein 4.2 / Electronmicroscopy / Morphogenesis / 赤血球膜 / 遺伝子解析 / 遺伝性球状赤血球症 / Band3 / Protein4.2 / 電顕学的検索 / 形態形成 / band 4.2 / band 3 / β-spectrin / 免疫電顕|
The following results were obtained for the recent two years (1995-1997) :
1. Hereditary spherocytosis :
(1) Ankyrin/spectrin anomalies appeared to be much less frequent in Japan, compared with those in Western countries.
(2) Four mutations in the band 3 gene in 50 HS patients and 11 polymorphism and one mutation in the ankyrin gene were detected in 50 normal subjects and 20 HS patients.
(3) A trait of HS carried a chromosomal anomaly of 8p.
2. Band 4.2 :
(1) Two novel mutations with complete band 4.2 deficiency were detected : (1) allele 4.2 Komatsu (523GAT*TAT) and allele 4.2 Shiga (317CGC*TGC).
(2) Marked derangements were observed on the intramembrane particles and the cytoskeletal network in the complete band 4.2 deficiencies by electron microscopy.
(3) Band 4.2 was proved to have a direct binding to spectrins.
(4) The pathogenesis of band 4.2 doublet Nagano was studied by biochemistry and molecular biology.
3. Band 3 :
(1) Complete band 3 deficiency was described as the first case in the world.
(2) Phenotypic characteristics were reported in homozygotes of band 3 Fukuoka.
(3) A combined deficiency of band 3 and glycophorin A was found as a membrane glycoprotein anomaly.
(4) Four novel mutations of band 3 gene were detected in band 3 Okinawa.
4. Morphogenesis of red cell membranes :
It was shown that the expression of membrane proteins in erythroid differentiation was initiated in spectrins, glycophorins and band 3, followed by band 4.1 and ankyrin, and completed by the expression of band 4.2 at the last stage of the differentiation.
5. Hereditary elliptocytosis :
(1) The gene defect was identified in beta-spectrin Natoya.
(2) Marked derangement of the intramembrane particles and the cytoskeletal network was observed by electron microscopy in red cells of the complete band 4.1 deficiency (allele 4.1 (-) Madrid).