Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.

Masato Ohtsuka,Shinichi Yoshimura,Hidetoshi Inoko,Jerzy K Kulski

doi:10.1186/1471-2164-9-178

Masato Ohtsuka, Shinichi Yoshimura + Show 2 more

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https://doi.org/10.1186/1471-2164-9-178

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Journal: BMC genomics	Publication Date: Jan 1, 2008
Citations: 108	License type: cc-by

Affiliation: Tokai University, University of Western Australia

Abstract

BackgroundThe 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.ResultsThe 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.ConclusionDuplicated 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.

Highlights

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
The class I molecules generally elicit immune responses by presenting peptide antigens derived from intracellular proteins to T lymphocytes and their genes can be classified into two groups, the classical Mhc class I genes and the non-classical Mhc class I genes
Expression patterns of each of the Mhc class Ib genes were examined by Reverse transcriptase-polymerase chain reaction (RTPCR) using gene-specific primer sets, and we identified Mhc class Ib genes with either tissue-restricted expression or tissue-wide expression

Summary

Introduction

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. The Major Histocompatibility Complex (MHC) genomic region harbors duplicated genes that express protein molecules responsible for the rejection of transplanted tissue, restricted antigen presentation and the recognition of self and non-self [1,2]. The classical Mhc class Ia genes, such as H2-K and -D in the mouse, are highly polymorphic, expressed widely and present antigens to CD8+ cytotoxic T cells. The non-classical class Ib molecules are structurally similar to the classical class Ia proteins, but in contrast to the classical class Ia proteins, they have limited or no polymorphisms They are more restricted in their tissue expression and some have functions other than antigen presentation to CD8+ T cells. The TL antigen is involved in the formation of memory CD8+ T cells [12] and in the regulation of iIEL responses in the intestine by interaction with homodimeric CD8 alpha receptors [13]

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