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Development of model animal to reveal the antibody production for ABO blood group antigens.

开发模型动物以揭示 ABO 血型抗原的抗体产生。

基本信息

批准号：
15590586
负责人：
IWAMOTO Sadahiko
金额：
$ 2.3万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590586/
关键词：
ABO transgenic rat transplantation ABO evolution rat ABO antigen 移植抗原ラットABHオーソログ

项目摘要

Histo-blood group ABH antigens are important not only for blood transfusion but also for organ transplantation. To improve the clinical management of transplantation, we have established transgenic rats expressing human A-transferase and B-transferase gene. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. When small intestines of wild Wistar were transplanted into A- or B-trangenic rats, the grafts were rapidly rejected compared to the grafts from A- or B-transgenic rats into wild. The systemic expression of A- or B-antigens may have modified the terminal organization of sugar chain antenna and have stimulated the innate-immune system. We have cloned authologous genes of ABO transferase from Wistar rat, which consisted of three A-transferase and one B-transferase genes. These cDNAs were mapped on rats genome draft sequence. Rat chromosome 1 accommodates B-transferase gene and chromosome 3 encodes tandem arrayed three A-transferase copies. These facts indicated that the A- and B-transferase genes were established as paralogous genes in some mammals. Primates encode single ABO gene. If the ABO ancestral genes consisted of multicopy genes with A and B transferase activity like rats, they must donate or accept gene fragments from each other and may produce a locus composed of A-alleles and B-alleles. The multicopy genes may possibly gather and bundle into a single gene through unequal cross over. This estimation must be resolved by further genome projects in other mammals.

组织血型ABH抗原不仅对输血很重要，而且对器官移植也很重要。为了改善移植的临床管理，我们建立了表达人a转移酶和b转移酶基因的转基因大鼠。野生Wistar大鼠唾液腺、肠和膀胱组织中表达a抗原，但b抗原未在任何器官中染色。a转基因大鼠在脑丛、II型肺上皮、胰腺和表皮的异位组织中表达a抗原。转b基因大鼠的b抗原与转a基因大鼠在相同器官中表达。将野生Wistar小肠移植到A-或b -转基因大鼠体内时，与将A-或b -转基因大鼠移植到野生大鼠体内相比，移植物会迅速产生排斥反应。A抗原或b抗原的系统表达可能修饰了糖链天线的末端组织，刺激了先天免疫系统。我们克隆了Wistar大鼠ABO转移酶的同源基因，包括3个a转移酶基因和1个b转移酶基因。这些cdna被定位到大鼠基因组草图序列上。大鼠1号染色体容纳b转移酶基因，3号染色体编码串联排列的3个a转移酶拷贝。这些事实表明，A-和b -转移酶基因在某些哺乳动物中被确定为同源基因。灵长类动物编码单个ABO基因。如果ABO祖先基因像大鼠一样由具有A和B转移酶活性的多拷贝基因组成，它们必须相互捐献或接受对方的基因片段，并可能产生由A等位基因和B等位基因组成的基因座。多拷贝基因可能通过不均匀杂交而聚集并捆绑成一个单一基因。这一估计必须通过其他哺乳动物的进一步基因组计划来解决。