Inaba Niro, Hiruma Toru, Togayachi Akira, Iwasaki Hiroko, Wang Xiao-Hui, Furukawa Yusuke, Sumi Ryoichi, Kudo Takashi, Fujimura Katsuya, Iwai Toshie, Gotoh Masanori, Nakamura Mitsuru, Narimatsu Hisashi
National Institute of Advanced Industrial Science and Technology, Glycogene Function Team, Research Center for Glycoscience, Tsukuba, Ibaraki, Japan.
Blood. 2003 Apr 1;101(7):2870-6. doi: 10.1182/blood-2002-09-2838. Epub 2002 Dec 5.
The human blood group i and I antigens are determined by linear and branched poly-N-acetyllactosamine structures, respectively. In erythrocytes, the fetal i antigen is converted to the adult I antigen by I-branching beta-1,6-N-acetylglucosaminyltransferase (IGnT) during development. Dysfunction of the I-branching enzyme may result in the adult i phenotype in erythrocytes. However, the I gene responsible for blood group I antigen has not been fully confirmed. We report here a novel human I-branching enzyme, designated IGnT3. The genes for IGnT1 (reported in 1993), IGnT2 (also presented in this study), and IGnT3 consist of 3 exons and share the second and third exons. Bone marrow cells preferentially expressed IGnT3 transcript. During erythroid differentiation using CD34(+) cells, IGnT3 was markedly up-regulated with concomitant decrease in IGnT1/2. Moreover, reticulocytes expressed the IGnT3 transcript, but IGnT1/2 was below detectable levels. By molecular genetic analyses of an adult i pedigree, individuals with the adult i phenotype were revealed to have heterozygous alleles with mutations in exon 2 (1006G>A; Gly336Arg) and exon 3 (1049G>A; Gly350Glu), respectively, of the IGnT3 gene. Chinese hamster ovary (CHO) cells transfected with each mutated IGnT3 cDNA failed to express I antigen. These findings indicate that the expression of the blood group I antigen in erythrocytes is determined by a novel IGnT3, not by IGnT1 or IGnT2.
人类血型i和I抗原分别由线性和分支状的多聚N-乙酰乳糖胺结构决定。在红细胞中，胎儿期的i抗原在发育过程中通过I分支β-1,6-N-乙酰氨基葡萄糖基转移酶（IGnT）转化为成人型I抗原。I分支酶功能异常可能导致红细胞出现成人i表型。然而，负责血型I抗原的I基因尚未得到充分证实。我们在此报告一种新型人类I分支酶，命名为IGnT3。IGnT1基因（1993年报道）、IGnT2基因（本研究也有介绍）和IGnT3基因均由3个外显子组成，且共享第二和第三个外显子。骨髓细胞优先表达IGnT3转录本。在使用CD34(+)细胞进行红系分化过程中，IGnT3显著上调，同时IGnT1/2表达下降。此外，网织红细胞表达IGnT3转录本，但IGnT1/2表达低于可检测水平。通过对一个成人i家系的分子遗传学分析发现，具有成人i表型的个体在IGnT3基因的外显子2（1006G>A；甘氨酸336精氨酸）和外显子3（1049G>A；甘氨酸350谷氨酸）分别存在杂合突变等位基因。转染每个突变IGnT3 cDNA的中国仓鼠卵巢（CHO）细胞均未能表达I抗原。这些发现表明，红细胞中血型I抗原的表达由新型IGnT3决定，而非由IGnT1或IGnT2决定。
