KELL BLOOD GROUP SYSTEM AND THE MCLEOD PHENOTYPE

KELL 血型系统和 MCLEOD 表型

• 批准号: 6110459
• 负责人: COLVIN M REDMAN
• 金额: $ 23.65万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110459
• 关键词: RNase protection assay; SDS polyacrylamide gel electrophoresis; blood group antigens; clinical research; enzyme activity; erythrocyte membrane; erythropoiesis; family genetics; flow cytometry; gene expression; gene mutation; gene rearrangement; genetic polymorphism; human genetic material tag; human subject; laboratory rabbit; molecular pathology; northern blottings; nucleic acid sequence; phenotype; polymerase chain reaction; protein structure; site directed mutagenesis; southern blotting; surface antigens; transfection

The Kell blood group is one of the major blood antigenic systems in human red cells. It is a complex system and currently over 20 alloantigens have been determined to be part of, or related to, this group. The Kell system is important in transfusion medicine because some of its antigens are strong immunogens and Kell antibodies can cause severe reactions if incompatible blood is transfused and also cause hemolytic disease in newborns due to fetomaternal immunizations. A variant Kell system phenotype, named McLeod, is characterized by weak Kell antigens, lack of an otherwise universal antigen, Kx, and grossly abnormal red cell morphology. McLeads also have accompanying late onset muscular dystrophy and neurological abnormalities. We have identified the proteins that carry Kell and Kx antigens and by molecular cloning have characterized the Kell gene. We now have the following objectives: 1) Having characterized the 19 exons and the flanking intron regions of the Kell gene we will determine the molecular basis of different Kell phenotypes. The phenotypes will be confirmed by surface-expression of antigens in transfected cells. This information will be applied in collaboration with Project 5, to devise clinically useful procedures for identification of Kell antigens and antibodies. Preliminary studies show that persons with the rare Ko(null) phenotype, who do not express any Kell antigens or have Kell protein on the red cell membranes, contain an mRNA with normal coding sequences. We will determine the reasons for lack of Kell proteins on the red cells of Ko(null) persons. 2) Kell protein has sequence and structural similarities with zinc neutral endopeptidases. We shall determine the enzymatic specificities of Kell protein and explore possible functions. 3) We will investigate the cellular mechanisms by which Kell is assembled on the plasma membrane with emphasis on the onset and levels of expression during erythropoiesis. 4) A candidate gene (XK) for the McLeod syndrome has been isolated. We will determine whether it expresses Kx surface- antigen and study the relation between Kell and XK.

凯尔血型是人类主要的血液抗原系统之一