Signaling advances from immunogenetics to immunogenomics 英文参考文献.docVIP

Minireview Signaling advances from immunogenetics to immunogenomics Mark Boothby Address: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. E-mail: Mark.boothby@ Published: 19 November 2003 Genome Biology 2003, 4:239 The electronic version of this article is the complete one and can be found online at /2003/4/12/239 ? 2003 BioMed Central Ltd Abstract Recent studies describe new genome-wide mutagenesis strategies, coupled with phenotypic screening, and demonstrate the power of such approaches to provide new insights into the genetics of the immune response. A spate of recent articles in Nature, Journal of Biology, and Immunity [1-4] herald the ripened fruit of mutagenic and genomic approaches to dissecting the molecular mecha- nisms of immunity. Genetics has long been of central impor- tance in elucidating the nature of immune responses, its roots extending at least as deeply as the establishment of systems for understanding histocompatibility and immune regulation. The ‘pre-genomic’ era produced insights into autoimmune-disease susceptibility using the non-obese diabetic (NOD) strain of mice [5]. Somatic-cell mutants unresponsive to interferons were generated and character- ized, thereby leading understanding of Jak-STAT signaling pathways [6-8]. The TLR4 gene was identified as the basis for lipopolysaccharide (LPS) unresponsiveness in C3H/HeJ mice [9], and a mutated NF-?B-inducing kinase gene was found to be the cause of the alymphoid (aly) mutant mouse strain [10]. Moving into the post-genomic era, these exciting precedents have inspired systematic attacks on the genera- tion and analysis of mutant mouse strains to achieve a greater saturation of the gene pool and screening of these strains for immune system phenotypes. Papers exemplifying each of several mutational a