Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.
Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.
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DOI：
10.1186/1471-2164-9-178
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发表时间：
2008-04-17
期刊：
影响因子：
4.4
通讯作者：
Yoshimura, Shinichi
中科院分区：
文献类型：
--
作者：
Ohtsuka, Masato;Inoko, Hidetoshi;Kulski, Jerzy K.;Yoshimura, Shinichi
小鼠有30多个主要组织相容性复合体（Mhc） Ib类基因，它们大多以不同的基因簇存在于17号染色体的H2区。尽管近年来Mhc研究的进展揭示了Mhc Ib类基因在免疫和非免疫系统中的独特作用，但许多Ib类基因的功能仍有待阐明。为了更好地理解Ib类分子的作用，我们对小鼠品系C57BL/6 H2区Ib类分子的基因复制、组织和表达模式进行了表征。分析了H2-Q、-T和-M区域的基因组组织，在这些区域内鉴定了21个Mhc Ib类转录基因。点图和系统发育分析表明，这些基因是由单基因和/或多基因重复事件产生的。为了研究这些基因在成体组织、胚胎和胎盘中的表达，我们使用基因特异性引物进行了RT-PCR基因表达谱分析。获得的组织范围和组织特异性基因表达模式表明，基因表达的变化可能取决于复制基因的基因组位置以及位点特异性机制。在簇的着丝粒端H2-T区域的基因比在端粒端的基因表达更广泛，尽管基因的同源物之间核苷酸序列相似，但其表达具有组织限制性。位于H2-Q， t和-M区域的重复Mhc类Ib基因在各种发育和成人组织中存在差异表达。我们的发现为进一步在特定组织（如大脑）中Mhc类Ib基因表达谱的功能验证研究奠定了基础。重复基因表达结果与基因组分析相结合，表明可能存在H2-T基因表达的远程调控和/或基因启动子或增强子区域的重要但尚未确定的核苷酸变化。由于Mhc基因组区域在小鼠品系中存在多样性，因此它应该是一个有用的模型区域，用于比较分析重复基因组织、进化和表达模式调控之间的关系。
The mouse has more than 30 Major histocompatibility complex (Mhc) class Ib genes, most of which exist in the H2 region of chromosome 17 in distinct gene clusters. Although recent progress in Mhc research has revealed the unique roles of several Mhc class Ib genes in the immune and non-immune systems, the functions of many class Ib genes have still to be elucidated. To better understand the roles of class Ib molecules, we have characterized their gene duplication, organization and expression patterns within the H2 region of the mouse strain C57BL/6. The genomic organization of the H2-Q, -T and -M regions was analyzed and 21 transcribed Mhc class Ib genes were identified within these regions. Dot-plot and phylogenetic analyses implied that the genes were generated by monogenic and/or multigenic duplicated events. To investigate the adult tissue, embryonic and placental expressions of these genes, we performed RT-PCR gene expression profiling using gene-specific primers. Both tissue-wide and tissue-specific gene expression patterns were obtained that suggest that the variations in the gene expression may depend on the genomic location of the duplicated genes as well as locus specific mechanisms. The genes located in the H2-T region at the centromeric end of the cluster were expressed more widely than those at the telomeric end, which showed tissue-restricted expression in spite of nucleotide sequence similarities among gene paralogs. Duplicated Mhc class Ib genes located in the H2-Q, -T and -M regions are differentially expressed in a variety of developing and adult tissues. Our findings form the basis for further functional validation studies of the Mhc class Ib gene expression profiles in specific tissues, such as the brain. The duplicated gene expression results in combination with the genome analysis suggest the possibility of long-range regulation of H2-T gene expression and/or important, but as yet unidentified nucleotide changes in the promoter or enhancer regions of the genes. Since the Mhc genomic region has diversified among mouse strains, it should be a useful model region for comparative analyses of the relationships between duplicated gene organization, evolution and the regulation of expression patterns.
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