Averdam Anne, Kuhl Heiner, Sontag Mario, Becker Tamara, Hughes Austin L, Reinhardt Richard, Walter Lutz
Department of Primate Genetics, German Primate Center, Göttingen, Germany.
J Immunol. 2007 Jun 1;178(11):7151-61. doi: 10.4049/jimmunol.178.11.7151.
The common marmoset monkey (Callithrix jacchus) is a New World primate that is increasingly used in biomedical research as a model organism. Due to the occurrence of natural bone marrow chimerism, it represents a particularly useful primate model in immunological research. In this study, we describe the genomic organization of the CD94, NKG2, and LY49L genes in the NK complex (NKC) of the common marmoset based on complete sequencing of a bacterial artificial chromosome clonal contig. This region of the marmoset NKC is 1.5 times smaller than its human counterpart, but the genes are colinear and orthologous. One exception is the activating NKG2CE gene, which is probably an ancestral form of the NKG2C- and NKG2E-activating receptor genes of humans and great apes. The two completely sequenced marmoset bacterial artificial chromosome clones are derived from distinct haplotypes, which differ by 200 sites in the overlapping sequence. Analyses of NKC genes in nine additional marmoset individuals revealed a moderate degree of polymorphism of the CD94, NKG2A, NKG2CE, and NKG2D genes. Furthermore, expression analyses identified several alternatively spliced transcripts, particularly of the CD94 gene. Several products of alternative splicing of NKC genes are highly conserved among primates. Alternative transcriptional start sites were found, but these probably do not lead to a change of the translational start site or result in longer or shorter cytoplasmic regions of these type II membrane receptors.
普通狨猴(Callithrix jacchus)是一种新大陆灵长类动物,越来越多地被用作生物医学研究中的模式生物。由于自然骨髓嵌合体的存在,它在免疫学研究中是一种特别有用的灵长类动物模型。在本研究中,我们基于细菌人工染色体克隆重叠群的全序列分析,描述了普通狨猴自然杀伤细胞复合体(NKC)中CD94、NKG2和LY49L基因的基因组组织。狨猴NKC的这一区域比人类的对应区域小1.5倍,但基因是共线且直系同源的。一个例外是激活型NKG2CE基因,它可能是人类和大猩猩NKG2C及NKG2E激活受体基因的祖先形式。两个完全测序的狨猴细菌人工染色体克隆来自不同的单倍型,在重叠序列中有200个位点不同。对另外9只狨猴个体的NKC基因分析显示,CD94、NKG2A、NKG2CE和NKG2D基因存在中度多态性。此外,表达分析鉴定出几种可变剪接转录本,尤其是CD94基因的。NKC基因的几种可变剪接产物在灵长类动物中高度保守。发现了可变转录起始位点,但这些可能不会导致翻译起始位点的改变,也不会导致这些II型膜受体的胞质区域变长或变短。