Adenosine deaminase (ADA) deficiency in cells derived from humans with severe combined immunodeficiency is due to an aberration of the ADA protein.
Adenosine deaminase (ADA) deficiency in cells derived from humans with severe combined immunodeficiency is due to an aberration of the ADA protein.
复制标题
患有严重联合免疫缺陷的人的细胞中腺苷脱氨酶 (ADA) 缺乏是由于 ADA 蛋白的畸变造成的。
DOI：
10.1093/nar/12.2.1015
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发表时间：
1984
影响因子：
14.9
通讯作者：
A. van der Eb
中科院分区：
文献类型：
--
作者：
D. Valerio;M. Duyvesteyn;H. van Ormondt;P. Meera Khan;A. van der Eb
为了确定重症联合免疫缺陷(SCID)患者细胞中腺苷脱氨酶(ADA)缺陷的分子基础，我们用人ADA基因克隆(1)分析了正常细胞和ADA-SCID细胞中ADA基因的组织和转录。在5个淋巴母细胞ADA-SCID细胞系中，我们没有检测到ADA基因及其侧翼序列的缺失或重排。此外，ADA-SCID细胞中ADA mRNA的合成和加工似乎是正常的，两个ADA-SCID细胞中的ADA特异性mRNA在体外可以被翻译成一种具有正常ADA分子量的蛋白质，而这种蛋白质在ADA抗血清中几乎不能沉淀。结果表明，在这两个ADA-SCID细胞系中，ADA活性的缺乏不是由于转录或翻译缺陷，而是由于蛋白质构型的微妙变化影响了其酶和免疫学特性。
In order to determine the molecular basis of adenosine deaminase (ADA) deficiency in cells derived from patients with severe combined immunodeficiency (SCID) disease, we used a human ADA cDNA clone (1) to analyse the organization and transcription of the ADA gene in both normal and ADA-SCID cells. In five lymphoblastoid ADA-SCID cell lines we could detect no deletions or rearrangements in the ADA gene and its flanking sequences. Furthermore, synthesis and processing of ADA mRNA appeared to be normal in the ADA-SCID cells, and ADA-specific mRNA from two ADA-SCID cells could be translated in vitro into a protein with the molecular weight of normal ADA; this protein, however, could hardly be precipitated with an ADA antiserum. The results indicate that in these two ADA-SCID cell lines, the lack of ADA activity is not due to transcriptional or translational defects, but to subtle changes in the configuration of the protein affecting both its enzymatic and immunological characteristics.