Molecular Genetics of Hereditary Red Cell Membrane Disorders

遗传性红细胞膜疾病的分子遗传学

• 批准号: 08044328
• 负责人: YAWATA Yoshihito
• 金额: $ 2.75万
• 依托单位: KAWASAKI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044328/
• 关键词: Red cell membrane; Cytoskeleton; Hereditary elliptocytosis; Molecular electron microscopy; Band 3; Band 4.1; Gene analysis; Hereditary spherocytosis

The follwing results were obtained under this research project in the academic year of 1996.1.Band 3 abnormalities :(1)In the Okinawa family with hereditary spherocytosis, three mutations ("(1)"K56E : AAG*GAG, "(2)"P854L : CCG*CTG, "(3)"G714R : GGG*AGG) were detected on the allele Okinawa, in addition to a mutation (G130R : GGA*AGA) in the other allele. The following results were obtained under this research project in the academic year of 1996. The compound mutations induced a total absence of protein 4.2 with a partial deficiency of band 3. Phenotypic characteristics in the red were studied by molecular bioligy, biochemical analysis and electron microscopy.(2)Complete band 3 deficiency in cattle was reported as the first case in this category. The trait suffered from marked acidosis, retarded growth, and striking microspherocytosis.2.Molecular electron microscopic studies on the impaired cytoskeletal network in complete deficiency of protein 4.1 (4.1 (-) Madrid) :Protein 4.1 was totally missing in the 4.1 (-) Madrid due to the mutation at the initiation codon (AUG), as previously reported by the French group (Prof. Jean Delaunay). It was proven that the cytoskeletal network was markedly distorted and disrupted by the total absence of protein 4.1 by electron microscopic analysis.Other results :Other novel cases of red cell membrane disorders were detected, especially on protein 4.2, and hereditary spherocytosis. The phenotypes and genotypes were clarified on these cases.

(1)在遗传性球形红细胞增多症冲绳家系中，除另一个等位基因(G130R：GGA*AGA)发生突变(G130R：GGA*AGA)外，还检测到K56E：AAG*Gag、P854L：CCG*CTG、G714R：GGG*agg等位基因突变。在该研究项目下，1996学年取得了以下成果。通过分子生物学、生化分析和电子显微镜等方法对红牛的表型特征进行了研究。(2)首次报道了黄牛完全缺乏带3的情况。2.蛋白质4.1完全缺乏时细胞骨架网络受损的分子电子显微镜研究(4.1(-)马德里)：正如法国研究小组(Jean Delaunay教授)先前报道的那样，在4.1(-)马德里，由于起始密码子(AUG)的突变，蛋白质4.1完全缺失。通过电子显微镜分析证明，蛋白质4.1的完全缺失使细胞骨架网络明显扭曲和破坏。其他结果：还发现了其他新病例，特别是蛋白质4.2和遗传性球形红细胞增多症。明确了这些病例的表型和基因分型。

项目成果

八幡愛弓: "赤血球膜蛋白band4.2のspectrin結合による骨格蛋白網上の局在の生化学的・免疫電顕的研究" Int.J.Hematol.63(Supple.1). 245- (1996)

Ayumi Yahata：“通过血影蛋白结合对红细胞膜蛋白带 4.2 在骨骼蛋白网络上的定位进行生化和免疫电子显微镜研究”Int.J.Hematol.63（Supple.1）。

Inaba, M., Yawata, A., Koshino, I., Sato, K., Takeuchi, M., Takakuwa, Y., Manno, S., Yawata, Y., Kanzaki, A., Sakai, J., Ban, A., Ono, K., Maede Y.: "Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total d

稻叶 M.、八幡 A.、小筱 I.、佐藤 K.、竹内 M.、高桑 Y.、曼野 S.、八幡 Y.、神崎 A.、酒井 J.、

Yawata, Y., Kanzaki, A., Inoue, T., Kaku, M., Yawata, A., Takezono, M., Shimodaira, Y., Ishida, F., Kobayashi, H.: "Posttranslational modification of protein 4.2 : A protein 4.2 doublet Nagano with its 72 and 74 KDs." Blood. 88(Suppl.1). 8b (1996)

Yawata，Y.，Kanzaki，A.，Inoue，T.，Kaku，M.，Yawata，A.，Takezono，M.，Shimodaira，Y.，Ishida，F.，Kobayashi，H.：“蛋白质的翻译后修饰

Yawata,A.: "A markedly disrupted skeletal network with abnormally distributed intramembrane particles in completed protein 4.1 deficient red cells (allele 4.1 Madrid): Implications regarding a critical role of protein 4.1 in maintenance of the integrity o

Yawata，A.：“在完整的蛋白质 4.1 缺陷红细胞（等位基因 4.1 马德里）中，骨骼网络明显破坏，膜内颗粒分布异常：关于蛋白质 4.1 在维持细胞完整性中的关键作用的影响

八幡義人: "わが国の赤血球膜異常症:遺伝生化学的・分子電顕学的・細胞生物学的解析" Angle. 8. 1-27 (1996)

Yoshito Yahata：“日本的红细胞膜异常：遗传生化、分子电子显微镜和细胞生物学分析”角度。8. 1-27 (1996)