Unraveling innate immunity using large scale N-ethyl-N-nitrosourea mutagenesis.
With the mouse genome almost entirely sequenced and readily accessible to all who wish to examine it, the challenge across most biological disciplines now lies in the decipherment of gene and protein function rather than in the realm of gene identification per se. In the field of innate immunity, forward genetic methods have repeatedly been applied to identify key sensors, adapters, and effector molecules. However, most spontaneous mutations that affect innate immune function have been mapped and cloned, and the need for new monogenic phenotypes has been felt evermore keenly. N-Ethyl-N-nitrosourea (ENU) mutagenesis is an efficient tool for the creation of aberrant monogenic innate immune response phenotypes. In this review, we will discuss the potential of the forward genetic approach and ENU mutagenesis to identify new genes and new functions of known genes related to innate immunity.
Hoebe
K
K
Department of Immunology IMM-31, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. khoebe@scripps.edu
Beutler
B
B
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology; D005038:Ethylnitrosourea / Q000494:pharmacology; D018390:Gene Targeting; D005808:Genes, Recessive; D005821:Genetic Techniques; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D053594:Myeloid Differentiation Factor 88; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D018955:CD36 Antigens; D005038:Ethylnitrosourea; D008562:Membrane Glycoproteins; D009153:Mutagens; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C434984:TIRAP protein, human; C499045:TIRAP protein, mouse