A CLUE TO THE BASIC DEFECT IN CYSTIC-FIBROSIS FROM CLONING THE CF-ANTIGEN GENE
A CLUE TO THE BASIC DEFECT IN CYSTIC-FIBROSIS FROM CLONING THE CF-ANTIGEN GENE
复制标题
DOI：
10.1038/326614a0
复制
发表时间：
1987-04-09
期刊：
影响因子：
64.8
通讯作者：
VANHEYNINGEN, V
中科院分区：
文献类型：
--
作者：
DORIN, JR;NOVAK, M;VANHEYNINGEN, V
常染色体隐性遗传病囊性纤维化（CF）的代谢基础仍然不明。CF纯合子和专性杂合子的血清蛋白水平升高已被描述1。由于杂合子在临床上不受影响，因此在这些个体中持续观察到的任何异常都可能是疾病病因的指针。这种血清蛋白的基因称为囊性纤维化（CF）抗原，已定位于1号染色体（参考文献2）。这不是CF中突变的基因，因为这已经通过CF家族中疾病与紧密连锁的DNA标记的共分离而被分配到7号染色体3 -5。CF抗原是正常和白血病粒细胞2的产物，并且在早幼粒细胞细胞系HL 60（M.N.，J.D.，C.海沃德，F.诺斯罗普，D JHB，步行者，货车H.和D.S.S.手稿正在准备中）。我们已经从慢性粒细胞白血病（CML）细胞的信使RNA构建的文库中分离出这种蛋白质的cDNA克隆。从cDNA克隆和通过mRNA的引物延伸获得完整的核苷酸序列。我们已经证实编码CF抗原的基因位于1号染色体上，并将其定位于特定区域。RNA印迹分析显示CML细胞和诱导的HL 60中的550-bp主要转录物。从核苷酸序列预测的氨基酸序列显示出显着的同源性与肠和脑钙结合蛋白。这种蛋白质在CF中的异常积累是一个线索，现在必须追求的证据正在收集，CF中的基本缺陷是在控制氯离子通道活性的途径6，7。
The metabolic basis of the autosomal recessive disease cystic fibrosis (CF) remains unidentified. Elevated levels of a serum protein in CF homozygotes and obligate heterozygotes have been described1. As heterozygotes are clinically unaffected, any consistently observed abnormality in these individuals is a likely pointer to the aetiology of the disease. The gene for this serum protein, called cystic fibrosis (CF) antigen, has been mapped to chromosome 1 (ref. 2). It is not the gene that is mutant in CF because this has since been assigned to chromosome 7 by cosegregation of the disease with closely linked DNA markers in CF families3–5. CF antigen is a product of normal and leukaemic granulocytes2and is inducible in the promyelocytic cell line HL60 (M.N., J.D., C. Hayward, F. Northrop, D J.H.B., J. Walker, V. van H. and D.S.S., manuscript in preparation). We have isolated cDNA clones for this protein from a library constructed with messenger RNA from chronic myeloid leukaemia (CML) cells. The complete nucleotide sequence was obtained from the cDNA clone and by primer extension of mRNA. We have confirmed that the gene encoding CF antigen is on chromosome 1 and have localized it to a particular region. RNA blot analysis shows a 550-bp major transcript in CML cells and in induced HL60. The ammo-acid sequence predicted from the nucleotide sequence shows significant homology with intestinal and brain calcium-binding proteins. Abnormal accumulation of such a protein in CF is a clue which must be pursued now that evidence is gathering that the basic defect in CF is in pathways controlling chloride channel activity6,7.