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与人类MAGE基因同源的三个小鼠基因的结构、染色体定位及表达模式

Structure, chromosomal location, and expression pattern of three mouse genes homologous to the human MAGE genes.

作者信息

De Backer O, Verheyden A M, Martin B, Godelaine D, De Plaen E, Brasseur R, Avner P, Boon T

机构信息

Ludwig Institute for Cancer Research, Belgium.

出版信息

Genomics. 1995 Jul 1;28(1):74-83. doi: 10.1006/geno.1995.1108.

DOI:10.1006/geno.1995.1108
PMID:7590750
Abstract

The human MAGE1 gene directs the expression of an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. MAGE1 belongs to a family of genes that are expressed in a number of tumors of various histological types but not in normal tissues except testis. The MAGE genes are arranged in two groups that are located within two different regions of the human X chromosome (Xq26-qter and Xp21.3). By hybridizing mouse genomic libraries with a MAGE1 probe, we identified three homologous genes. Two of these mouse genes, Smage1 and Smage2, are more than 99% identical to each other and encode the same protein of 330 aa. The 5' noncoding region of Smage2 provides the potential for regulating the expression of the gene through several different promoters located in front of alternative first exons. The third gene, Smage3, has the structure of a processed transcript. It codes for a protein with only 11 aa substitutions with respect to the Smage1/2 product. Somatic cell hybrids and interspecific backcross analysis showed that Smage3 is autosomal and that Smage1 and Smage2 are located between the Dmd and the Ar loci on the mouse X chromosome. Since this region is syntenic to the human Xp21.1-p22.1 region, we conclude that Smage1 and Smage2 are homologous to the MAGE-Xp rather than to the MAGE-Xq genes. Smage1/2 transcripts were detected in several tumor and embryonal cell lines but not in normal mouse tissues with the exception of testis. Expression of Smage3 was found in embryos from Day 11 to Day 15.

摘要

人类MAGE1基因指导一种抗原的表达,该抗原可被自体溶细胞性T淋巴细胞识别,存在于黑色素瘤中。MAGE1属于一个基因家族,该家族基因在多种组织学类型的多种肿瘤中表达,但除睾丸外不在正常组织中表达。MAGE基因分为两组,位于人类X染色体的两个不同区域(Xq26 - qter和Xp21.3)。通过用MAGE1探针与小鼠基因组文库杂交,我们鉴定出三个同源基因。其中两个小鼠基因,Smage1和Smage2,彼此间的同源性超过99%,编码相同的330个氨基酸的蛋白质。Smage2的5'非编码区通过位于可变第一外显子前面的几个不同启动子提供了调节基因表达的潜力。第三个基因Smage3具有加工转录本的结构。它编码的蛋白质相对于Smage1/2产物只有11个氨基酸的替换。体细胞杂种和种间回交分析表明,Smage3是常染色体基因,而Smage1和Smage2位于小鼠X染色体上的Dmd和Ar基因座之间。由于该区域与人类Xp21.1 - p22.1区域同线,我们得出结论,Smage1和Smage2与MAGE - Xp基因同源,而不是与MAGE - Xq基因同源。在几种肿瘤和胚胎细胞系中检测到了Smage1/2转录本,但除睾丸外,在正常小鼠组织中未检测到。在第11天到第15天的胚胎中发现了Smage3的表达。

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