Hardiman G, Jenkins N A, Copeland N G, Gilbert D J, Garcia D K, Naylor S L, Kastelein R A, Bazan J F
Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304-1104, USA.
Genomics. 1997 Oct 15;45(2):332-9. doi: 10.1006/geno.1997.4940.
The myeloid differentiation (MyD) marker MyD88 was initially characterized as a primary response gene, upregulated in mouse M1 myeloleukemic cells in response to differentiation induced by interleukin-6. Subsequent analysis revealed that MyD88 possesses a unique modular structure, which consists of an N-terminal "death domain," similar to the intracellular segments of TNF receptor 1 and Fas, and a C-terminal region related to the cytoplasmic domains of the Drosophila morphogen Toll and vertebrate interleukin-1 receptors. In this report we describe the cloning and gene structure of mouse MyD88. The complete coding sequence of mouse MyD88 spans five exons, with the first exon encoding the complete death domain. Zooblot analysis revealed that MyD88 is an evolutionarily conserved gene. MyD88 was localized to the distal region of mouse chromosome 9 by interspecific backcross mapping. The human homolog (hMyD88) was mapped to chromosome 3p22-p21.3 by PCR analysis of a human chromosome 3 somatic cell hybrid mapping panel. Northern blot analysis revealed widespread expression of MyD88 in many adult mouse tissues, and RT-PCR studies detected MyD88 mRNA in T and B cell lines and differentiating embryonic stem cells. The broad expression pattern demonstrates that mouse MyD88 expression is not restricted to cells of myeloid lineage as was originally believed.
髓样分化（MyD）标志物MyD88最初被鉴定为一个初级反应基因，在小鼠M1骨髓白血病细胞中，受白细胞介素-6诱导分化时表达上调。随后的分析表明，MyD88具有独特的模块化结构，它由一个N端“死亡结构域”和一个C端区域组成，N端“死亡结构域”类似于肿瘤坏死因子受体1和Fas的细胞内片段，C端区域与果蝇形态发生素Toll及脊椎动物白细胞介素-1受体的胞质结构域相关。在本报告中，我们描述了小鼠MyD88的克隆及基因结构。小鼠MyD88的完整编码序列跨越5个外显子，第一个外显子编码完整的死亡结构域。动物杂交印迹分析表明，MyD88是一个进化上保守的基因。通过种间回交定位，将MyD88定位于小鼠9号染色体的远端区域。通过对人3号染色体体细胞杂种定位板进行PCR分析，将人同源物（hMyD88）定位于3p22 - p21.3。Northern印迹分析显示，MyD88在许多成年小鼠组织中广泛表达，RT-PCR研究在T和B细胞系以及分化的胚胎干细胞中检测到MyD88 mRNA。这种广泛的表达模式表明，小鼠MyD88的表达并不像最初认为的那样仅限于髓系细胞。
