Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Immunogenetics. 2011 Mar;63(3):183-7. doi: 10.1007/s00251-011-0511-2. Epub 2011 Jan 18.
Nwc represents a mysterious third evolutionarily conserved gene within the Rag locus. Here, we analyzed the phenotype of Nwc(tmpro1) mice, in which the Rag2 intragenic region containing the previously identified promoter responsible for initiating transcription of Nwc in all cells except lymphocytes was deleted by homologous recombination. Despite strong nonlymphocyte-specific inhibition of Nwc transcription which runs through the regulatory region of Rag genes, their expression remained suppressed, and no developmental, morphological, anatomical, functional, physiological, or cellular defects in Nwc(tmpro1) mice could be observed. However, careful analysis of the Rag2 intergenic region uncovered a second evolutionarily conserved Nwc promoter region from which a previously unknown Nwc transcript can be generated in nonlymphocytes of Nwc(tmpro1) and normal mice. The above results reveal an unexpected additional complexity of transcriptional regulation within the Rag/Nwc locus and show that strong inhibition of Nwc transcription in nonlymphoid cells is well tolerated. Complete inactivation of Nwc is necessary to get insight into its function at transcriptional and posttranscriptional levels.
Nwc 代表 Rag 基因座内一个神秘的第三个进化保守基因。在这里，我们分析了 Nwc(tmpro1) 小鼠的表型，其中 Rag2 基因内区通过同源重组缺失了先前鉴定的负责启动除淋巴细胞以外所有细胞中 Nwc 转录的启动子。尽管 Nwc 转录的非淋巴细胞特异性强烈抑制贯穿 Rag 基因的调控区，但它们的表达仍然受到抑制，在 Nwc(tmpro1) 小鼠中没有观察到发育、形态、解剖、功能、生理或细胞缺陷。然而，对 Rag2 基因间区的仔细分析揭示了第二个进化保守的 Nwc 启动子区域，从该区域可以在 Nwc(tmpro1) 和正常小鼠的非淋巴细胞中产生先前未知的 Nwc 转录本。上述结果揭示了 Rag/Nwc 基因座内转录调控的意外额外复杂性，并表明非淋巴样细胞中 Nwc 转录的强烈抑制是可以耐受的。完全失活 Nwc 是深入了解其在转录和转录后水平的功能所必需的。
