Genomes and Genes
rag 1 genes
Summary: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.
- Smith J, Grizot S, Arnould S, Duclert A, Epinat J, Chames P, et al. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res. 2006;34:e149 pubmed..These results demonstrate that the plasticity of LAGLIDADG endonucleases allows extensive engineering, and provide a general method to create novel endonucleases with tailored specificities. ..
- Groth J, Barrowclough G. Basal divergences in birds and the phylogenetic utility of the nuclear RAG-1 gene. Mol Phylogenet Evol. 1999;12:115-23 pubmed..However, RAG-1 does not evolve in a clocklike manner, suggesting that this gene cannot easily be used for estimating ages of ancient lineages. ..
- Tsai C, Drejer A, Schatz D. Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes Dev. 2002;16:1934-49 pubmed..Our results suggest that the RAG proteins have an architectural function in facilitating proper and efficient V(D)J joining, and a protective function in preventing degradation of broken ends prior to joining. ..
- Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu Rev Biochem. 2002;71:101-32 pubmed..This transposition helps to explain the mechanism of RAG action and supports earlier proposals that V(D)J recombination evolved from an ancient mobile DNA element. ..
- Lambolez F, Azogui O, Joret A, Garcia C, von Boehmer H, Di Santo J, et al. Characterization of T cell differentiation in the murine gut. J Exp Med. 2002;195:437-49 pubmed..Finally, only 3% of CP cells were clearly involved in T cell differentiation, suggesting that these structures may have additional physiological roles in the gut. ..
- Maraskovsky E, O Reilly L, Teepe M, Corcoran L, Peschon J, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell. 1997;89:1011-9 pubmed..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2. ..
- McBlane J, van Gent D, Ramsden D, Romeo C, Cuomo C, Gellert M, et al. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell. 1995;83:387-95 pubmed..The hairpin is made as a direct consequence of the cleavage mechanism. Nicking and hairpin formation each require the presence of a signal sequence and both RAG proteins. ..
- Spanopoulou E, Roman C, Corcoran L, Schlissel M, Silver D, Nemazee D, et al. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 1994;8:1030-42 pubmed..These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process. ..
- Mombaerts P, Clarke A, Rudnicki M, Iacomini J, Itohara S, Lafaille J, et al. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992;360:225-31 pubmed..TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta. ..
- Ardouin L, Ismaili J, Malissen B, Malissen M. The CD3-gammadeltaepsilon and CD3-zeta/eta modules are each essential for allelic exclusion at the T cell receptor beta locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-beta, -gamma, and -delta loci. J Exp Med. 1998;187:105-16 pubmed..Thus, the CD3 components are differentially involved in the sequential events that make the TCR-beta locus first accessible to, and later insulated from, the action of the V(D)J recombinase. ..
- Yu W, Misulovin Z, Suh H, Hardy R, Jankovic M, Yannoutsos N, et al. Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2. Science. 1999;285:1080-4 pubmed..This observation suggests a mechanism by which asymmetrically disposed cis DNA elements could influence the expression of the primordial transposon and thereby capture RAGs for vertebrate evolution. ..
- Roman C, Cherry S, Baltimore D. Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a requirement for novel elements in the N-terminus of RAG-1. Immunity. 1997;7:13-24 pubmed..Our data suggest that the RAG-1 N-terminus enhances the formation of an active recombination complex that facilitates the rearrangement process. ..
- Pâques F, Duchateau P. Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy. Curr Gene Ther. 2007;7:49-66 pubmed..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient. ..
- Szabo P, Shen S, Telford W, Weksler M. Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice. Cell Immunol. 2003;222:78-87 pubmed..These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery. ..
- Ait Azzouzene D, Verkoczy L, Peters J, Gavin A, Skog P, VELA J, et al. An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system. J Exp Med. 2005;201:817-28 pubmed..We also demonstrate the unique advantages of our model in the genetic and cellular analysis of immune tolerance. ..
- Li J, Iwanami N, Hoa V, Furutani Seiki M, Takahama Y. Noninvasive intravital imaging of thymocyte dynamics in medaka. J Immunol. 2007;179:1605-15 pubmed..Thus, transgenic medaka enables real-time intravital imaging of thymocytes without surgical invasion. ..
- Jasinski J, Yu L, Nakayama M, Li M, Lipes M, Eisenbarth G, et al. Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout. Diabetes. 2006;55:1978-84 pubmed..scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis. ..
- Aidinis V, Plows D, Haralambous S, Armaka M, Papadopoulos P, Kanaki M, et al. Functional analysis of an arthritogenic synovial fibroblast. Arthritis Res Ther. 2003;5:R140-57 pubmed..Our findings support an aggressive role for the SF in the development of the disease and reinforce the perspective of a transformed-like character of the SF. ..
- Vaitaitis G, Poulin M, Sanderson R, Haskins K, Wagner D. Cutting edge: CD40-induced expression of recombination activating gene (RAG) 1 and RAG2: a mechanism for the generation of autoaggressive T cells in the periphery. J Immunol. 2003;170:3455-9 pubmed..Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells. ..
- Bentzien F, Struman I, Martini J, Martial J, Weiner R. Expression of the antiangiogenic factor 16K hPRL in human HCT116 colon cancer cells inhibits tumor growth in Rag1(-/-) mice. Cancer Res. 2001;61:7356-62 pubmed..These findings support the potential of 16K hPRL as a therapeutic agent for the treatment of colorectal cancer. ..
- Sikes M, Meade A, Tripathi R, Krangel M, Oltz E. Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility. Proc Natl Acad Sci U S A. 2002;99:12309-14 pubmed..These spatial constraints on promoter positioning may reflect an RNA polymerase-independent mechanism to target adjacent gene segments for chromatin remodeling events that facilitate rearrangement. ..
- Geurgas S, Rodrigues M, Moritz C. The genus Coleodactylus (Sphaerodactylinae, Gekkota) revisited: a molecular phylogenetic perspective. Mol Phylogenet Evol. 2008;49:92-101 pubmed publisher..3+/-4.33 Mya). Most intraspecific cladogenesis occurred through Miocene to Pliocene, and only for two conspecific samples and for C. natalensis could a Quaternary differentiation be assumed (1.9+/-1.3 Mya). ..
- Kim K, Bellendir S, Hudson K, Hill C, Hartman G, Hyten D, et al. Fine mapping the soybean aphid resistance gene Rag1 in soybean. Theor Appl Genet. 2010;120:1063-71 pubmed publisher..Several candidate genes for Rag1 are present within the 115-kb interval. The markers identified in this study that are closely linked to Rag1 will be a useful resource in MAS for this important aphid resistance gene. ..
- Chen J, Shinkai Y, Young F, Alt F. Probing immune functions in RAG-deficient mice. Curr Opin Immunol. 1994;6:313-9 pubmed
- Fleming S, Tsokos G. Complement, natural antibodies, autoantibodies and tissue injury. Autoimmun Rev. 2006;5:89-92 pubmed..Our experiments demonstrate that naturally occurring antibodies and autoantibodies mediate tissue injury only after an organ has been subjected to a stressor such as ischemia. ..
- Schuetz C, Huck K, Gudowius S, Megahed M, Feyen O, Hubner B, et al. An immunodeficiency disease with RAG mutations and granulomas. N Engl J Med. 2008;358:2030-8 pubmed publisher..In each case, both parents were heterozygous carriers of a RAG mutation. The mutations were associated with reduced function of RAG in vitro (3 to 30% of normal activity). The parents and one sibling in the three families were healthy. ..
- Shoo L, Rose R, Doughty P, Austin J, Melville J. Diversification patterns of pebble-mimic dragons are consistent with historical disruption of important habitat corridors in arid Australia. Mol Phylogenet Evol. 2008;48:528-42 pubmed publisher..Additional genetic structuring in the absence of recognized barriers suggests that an expanded view of potential habitat barriers in the arid zone is required. ..
- Munderloh U, Silverman D, MacNamara K, Ahlstrand G, Chatterjee M, Winslow G. Ixodes ovatus Ehrlichia exhibits unique ultrastructural characteristics in mammalian endothelial and tick-derived cells. Ann N Y Acad Sci. 2009;1166:112-9 pubmed publisher..IOE from RF/6A cells, when inoculated into C57BL/6 and RAG-deficient mice, induced fatal disease. These data reveal unique structural features of IOE that may contribute to the pathogen's high virulence. ..
- Schmid C, Stienekemeier M, Oehen S, Bootz F, Zielasek J, Gold R, et al. Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance. J Neurosci. 2000;20:729-35 pubmed..We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy. ..
- Bufalino A, Mayden R. Molecular phylogenetics of North American phoxinins (Actinopterygii: Cypriniformes: Leuciscidae) based on RAG1 and S7 nuclear DNA sequence data. Mol Phylogenet Evol. 2010;55:274-83 pubmed publisher..Most analyses recovered a strongly supported shiner clade though, similar to several mtDNA studies; there was a high degree of topological variability among the results. ..
- Haq I, Steinberg L, Hoenig M, van der Burg M, Villa A, Cant A, et al. GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B- SCID in patients with defects in RAG genes. Clin Immunol. 2007;124:165-9 pubmed..No significant differences in allele frequencies were found between the groups, and no trends identified. The mechanisms determining the OS or T-B-NK+ SCID phenotype remain to be determined. ..
- Evans B, Kelley D, Melnick D, Cannatella D. Evolution of RAG-1 in polyploid clawed frogs. Mol Biol Evol. 2005;22:1193-207 pubmed..Because of this, gene ancestry could potentially influence gene fate: interacting paralogs derived from the same lower ploidy ancestor might have similar genetic destinies. ..
- San Mauro D, Vences M, Alcobendas M, Zardoya R, Meyer A. Initial diversification of living amphibians predated the breakup of Pangaea. Am Nat. 2005;165:590-9 pubmed
- Taylor M, Hellberg M. Marine radiations at small geographic scales: speciation in neotropical reef gobies (Elacatinus). Evolution. 2005;59:374-85 pubmed..Overall, speciation in Elacatinus is consistent with a model of recurring adaptive radiations in stages taking place at small geographic scales. ..
- Schatz D, Chun J. V(D)J recombination and the transgenic brain blues. New Biol. 1992;4:188-96 pubmed
- Zuccon D, Cibois A, Pasquet E, Ericson P. Nuclear and mitochondrial sequence data reveal the major lineages of starlings, mynas and related taxa. Mol Phylogenet Evol. 2006;41:333-44 pubmed..The congruence between the age of major clades, estimated by NPRS, and palaeoclimatic data present evidence for the role of climatic changes in shaping present day distribution of the group...
- Lemaire M, Wésolowski Louvel M. Enolase and glycolytic flux play a role in the regulation of the glucose permease gene RAG1 of Kluyveromyces lactis. Genetics. 2004;168:723-31 pubmed..Therefore, it seems that the enolase and a functional glycolytic flux are necessary for induction of expression of the Rag1 glucose permease in K. lactis. ..
- Buckley R. Advances in the understanding and treatment of human severe combined immunodeficiency. Immunol Res. 2000;22:237-51 pubmed..5 mo of life, making early diagnosis crucial. Recently, gene therapy has also been successful in infants with X-linked SCID. ..
- Baker A, Pereira S, Haddrath O, Edge K. Multiple gene evidence for expansion of extant penguins out of Antarctica due to global cooling. Proc Biol Sci. 2006;273:11-7 pubmed..Thus, global cooling has had a major impact on penguin evolution, as it has on vertebrates generally. Penguins only reached cooler tropical waters in the Galapagos about 4 mya, and have not crossed the equatorial thermal barrier. ..
- Durum S, Candeias S, Nakajima H, Leonard W, Baird A, Berg L, et al. Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med. 1998;188:2233-41 pubmed..This data supports the model that IL-7R promotes TCR-gamma gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus. ..
- Ericson P, Envall I, Irestedt M, Norman J. Inter-familial relationships of the shorebirds (Aves: Charadriiformes) based on nuclear DNA sequence data. BMC Evol Biol. 2003;3:16 pubmed..The presented phylogenetic hypothesis provides a solid framework for analyses of macroevolution of ecological, morphological and behavioural adaptations observed within the order Charadriiformes. ..
- Diefenbach A, Hsia J, Hsiung M, Raulet D. A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity. Eur J Immunol. 2003;33:381-91 pubmed..Tumor cells ectopically expressing the molecule were efficiently rejected by naive mice, and induced strong protective immunity to the parental, ligand-negative tumor cells. ..
- Brandt V, Roth D. A recombinase diversified: new functions of the RAG proteins. Curr Opin Immunol. 2002;14:224-9 pubmed
- Peterson D, McNulty N, Guruge J, Gordon J. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe. 2007;2:328-39 pubmed..Immunoselection of bacterial epitope expression may contribute to the remarkable strain-level diversity in this ecosystem. ..
- Su D, Manley N. Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice. BMC Immunol. 2002;3:12 pubmed..We also observed a decrease in the level of the cytokines IL-7 and SCF produced by Hoxa3+/-Pax1-/-TECs. Our results indicate complex and stage-specific effects of abnormal TEC development on thymocyte proliferation. ..
- Villa A, Sobacchi C, Notarangelo L, Bozzi F, Abinun M, Abrahamsen T, et al. V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood. 2001;97:81-8 pubmed
- Villa A, Sobacchi C, Vezzoni P. Recombination activating gene and its defects. Curr Opin Allergy Clin Immunol. 2001;1:491-5 pubmed
- Taylor M, Hellberg M. Comparative phylogeography in a genus of coral reef fishes: biogeographic and genetic concordance in the Caribbean. Mol Ecol. 2006;15:695-707 pubmed..Our results, coupled with genetic and demographic data from other reef fishes and corals, provide robust support for the Mona Passage as a long-term biogeographic barrier for Caribbean animals. ..
- Carpenter A, Bassing C. Fetal thymocyte development: putting a zinc finger on it?. Nat Immunol. 2006;7:1285-6 pubmed
- Hu H, Wang B, Borde M, Nardone J, Maika S, Allred L, et al. Foxp1 is an essential transcriptional regulator of B cell development. Nat Immunol. 2006;7:819-26 pubmed..Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis. ..
- Berghoff M, Samsam M, Müller M, Kobsar I, Toyka K, Kiefer R, et al. Neuroprotective effect of the immune system in a mouse model of severe dysmyelinating hereditary neuropathy: enhanced axonal degeneration following disruption of the RAG-1 gene. Mol Cell Neurosci. 2005;28:118-27 pubmed..These data suggest a neuroprotective net effect of T-lymphocytes on axon survival in inherited, early onset dysmyelination. ..
- Muljo S, Schlissel M. The variable, C(H)1, C(H)2 and C(H)3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice. Int Immunol. 2002;14:577-84 pubmed..These findings lead us to suggest that the majority of the extracellular region of the pre-BCR is not required for pre-BCR function and, thus, ligand binding is unlikely to be required for pre-BCR function. ..
- Fort M, Leach M, Rennick D. A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis. J Immunol. 1998;161:3256-61 pubmed..Thus NK cells can play an important role in down-regulating Thl-mediated colitis by controlling the responses of effector T cells to gut bacteria. ..