Genomes and Genes
Gene Symbol: Rag2
Description: recombination activating gene 2
Alias: Rag-2, V(D)J recombination-activating protein 2, recombinase activating gene 2
- Cebrat M, Miazek A, Kisielow P. Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulation. Eur J Immunol. 2005;35:2230-8 pubmedRecombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements...
- Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol. 2010;11:171-9 pubmed publisher..Hence, STAT5 and IL-7 signaling control cell survival and the developmental ordering of immunoglobulin gene rearrangements by suppressing premature Igk recombination in pro-B cells. ..
- Rankin L, Groom J, Chopin M, Herold M, Walker J, Mielke L, et al. The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway. Nat Immunol. 2013;14:389-95 pubmed publisher..Our results pinpoint the regulation of Notch signaling by T-bet as a distinct molecular pathway that guides the development of NKp46+ ILCs...
- Powell N, Walker A, Stolarczyk E, Canavan J, Gökmen M, Marks E, et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity. 2012;37:674-84 pubmed publisher..IL-17A)-producing IL-7R?(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice...
- Price A, Liang H, Sullivan B, Reinhardt R, Eisley C, Erle D, et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci U S A. 2010;107:11489-94 pubmed publisher..Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses. ..
- Possot C, Schmutz S, Chea S, Boucontet L, Louise A, Cumano A, et al. Notch signaling is necessary for adult, but not fetal, development of ROR?t(+) innate lymphoid cells. Nat Immunol. 2011;12:949-58 pubmed publisher..Therefore, fetal and adult environments influence the differentiation of ROR?t(+) cells differently. ..
- Banh C, Miah S, Kerr W, Brossay L. Mouse natural killer cell development and maturation are differentially regulated by SHIP-1. Blood. 2012;120:4583-90 pubmed publisher..Taken together, our results provide novel insights on how SHIP-1 participates in the development, maturation, and effector functions of NK cells. ..
- Lin J, Li P, Liu D, Jin H, He J, Ata Ur Rasheed M, et al. Critical Role of STAT5 transcription factor tetramerization for cytokine responses and normal immune function. Immunity. 2012;36:586-99 pubmed publisher..Thus, tetramerization of STAT5 is critical for cytokine responses and normal immune function, establishing a critical role for STAT5 tetramerization in vivo. ..
- Chang Y, Kim H, Albacker L, Baumgarth N, McKenzie A, Smith D, et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol. 2011;12:631-8 pubmed publisher..Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13. ..
- Rathinam C, Poueymirou W, Rojas J, Murphy A, Valenzuela D, Yancopoulos G, et al. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood. 2011;118:3119-28 pubmed publisher..Insertion of human CSF1 into the corresponding mouse locus of Balb/c Rag2(-/-) ?c(-/-) mice through VELOCIGENE technology resulted in faithful expression of human CSF-1 in these mice both ..
- Ramadani F, Bolland D, Garcon F, Emery J, Vanhaesebroeck B, Corcoran A, et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci Signal. 2010;3:ra60 pubmed publisher..These studies indicate that either p110alpha or p110delta can mediate tonic signaling from the BCR, but only p110delta can contribute to antigen-dependent activation of B cells. ..
- Oboki K, Ohno T, Kajiwara N, Arae K, Morita H, Ishii A, et al. IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U S A. 2010;107:18581-6 pubmed publisher..These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses. ..
- Thomas S, Scanlon S, Griewank K, Constantinides M, Savage A, Barr K, et al. PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions. J Exp Med. 2011;208:1179-88 pubmed publisher..These findings reveal the unique genetic and biochemical pathway that underlies the innate intravascular surveillance program of NKT cells. ..
- Ebert A, McManus S, Tagoh H, Medvedovic J, Salvagiotto G, Novatchkova M, et al. The distal V(H) gene cluster of the Igh locus contains distinct regulatory elements with Pax5 transcription factor-dependent activity in pro-B cells. Immunity. 2011;34:175-87 pubmed publisher..The pro-B cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal V(H)-DJ(H) recombination at the Igh locus. ..
- Mishra B, Rathinam V, Martens G, Martinot A, Kornfeld H, Fitzgerald K, et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1?. Nat Immunol. 2013;14:52-60 pubmed publisher..Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections. ..
- Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy A, et al. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A. 2011;108:2378-83 pubmed publisher..We generated RAG2(-/-)?(c)(-/-) mice in which we replaced the gene encoding mouse TPO by its human homolog...
- Daussy C, Faure F, Mayol K, Viel S, Gasteiger G, Charrier E, et al. T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow. J Exp Med. 2014;211:563-77 pubmed publisher..Thus, mutually exclusive expression of T-bet and Eomes drives the development of different NK cell lineages with complementary functions. ..
- Schuster C, Berger A, Hoelzl M, Putz E, Frenzel A, Simma O, et al. The cooperating mutation or "second hit" determines the immunologic visibility toward MYC-induced murine lymphomas. Blood. 2011;118:4635-45 pubmed publisher..Our findings provide first evidence that the nature of the second hit affects tumor immunosurveillance in c-MYC-driven lymphomas and define a potential shortcoming of antitumor therapies targeting BCL-2. ..
- Furusawa J, Moro K, Motomura Y, Okamoto K, Zhu J, Takayanagi H, et al. Critical role of p38 and GATA3 in natural helper cell function. J Immunol. 2013;191:1818-26 pubmed publisher..However, deletion of either GATA3 or ROR? in hematopoietic stem cells severely blocked the development into NH cells. Our results demonstrate the important roles of p38 and GATA3 in NH cell functions. ..
- Deriano L, Chaumeil J, Coussens M, Multani A, Chou Y, Alekseyenko A, et al. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature. 2011;471:119-23 pubmed publisherMisrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice...
- Yurchenko E, Levings M, Piccirillo C. CD4+ Foxp3+ regulatory T cells suppress ?? T-cell effector functions in a model of T-cell-induced mucosal inflammation. Eur J Immunol. 2011;41:3455-66 pubmed publisher..Thus, functional alterations in T(REG) cells provoke dysregulated CD4(+) and ?? T-cell responses to commensal antigens in the intestine. ..
- Wong S, Walker J, Jolin H, Drynan L, Hams E, Camelo A, et al. Transcription factor ROR? is critical for nuocyte development. Nat Immunol. 2012;13:229-36 pubmed publisher..Notably, the transcription factor ROR? was critical for the development of nuocytes and their role in the expulsion of parasitic worms...
- Laszkiewicz A, Cebrat M, Miazek A, Kisielow P. Complexity of transcriptional regulation within the Rag locus: identification of a second Nwc promoter region within the Rag2 intron. Immunogenetics. 2011;63:183-7 pubmed publisher..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 ..
- Kollmann K, Heller G, Ott R, Scheicher R, Zebedin Brandl E, Schneckenleithner C, et al. c-JUN promotes BCR-ABL-induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6. Blood. 2011;117:4065-75 pubmed publisher..Moreover, we identify CDK6 as relevant and critical target of AP-1-regulated DNA methylation on BCR-ABL-induced transformation, thereby accelerating leukemogenesis. ..
- Weber B, Saurer L, Schenk M, Dickgreber N, Mueller C. CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. Eur J Immunol. 2011;41:773-9 pubmed publisher..CX3CR1(+) iMNP can further be subdivided based on differential expression of CX3CR1. Using CX3CR1(GFP/+) ×RAG2(-/-) mice, we demonstrate that CX3CR1(hi) and CX3CR1(lo) iMNP clearly differ with respect to their morphological ..
- Willinger T, Rongvaux A, Takizawa H, Yancopoulos G, Valenzuela D, Murphy A, et al. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci U S A. 2011;108:2390-5 pubmed publisher..The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens. ..
- Vaeth M, Gogishvili T, Bopp T, Klein M, Berberich Siebelt F, Gattenloehner S, et al. Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). Proc Natl Acad Sci U S A. 2011;108:2480-5 pubmed publisher..These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction. ..
- Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, et al. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci U S A. 2011;108:13218-23 pubmed publisher..NOD/scid/?(c)(-/-) (NSG) and BALB/c Rag2(-/-)?(c)(-/-) mice are the most commonly used mouse strains for this purpose and a number of studies have ..
- O Sullivan T, Dunn G, LACOURSIERE D, Schreiber R, Bui J. Cancer immunoediting of the NK group 2D ligand H60a. J Immunol. 2011;187:3538-45 pubmed publisher..In one of these cell lines, the H60a-hi cells could be removed by passaging the cells through RAG2(-/-) mice, resulting in edited cell lines that were poor targets for NK cells and that displayed progressive tumor ..
- Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz D. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell. 2010;141:419-31 pubmed publisherThe critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo...
- Johnson K, Chaumeil J, Micsinai M, Wang J, Ramsey L, Baracho G, et al. IL-7 functionally segregates the pro-B cell stage by regulating transcription of recombination mediators across cell cycle. J Immunol. 2012;188:6084-92 pubmed publisher..One established mechanism of regulation is through periodic degradation of the RAG2 recombinase protein. However, there are additional levels of protection...
- Zhang L, Reynolds T, Shan X, Desiderio S. Coupling of V(D)J recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis. Immunity. 2011;34:163-74 pubmed publisher..We infer that cell cycle control of the V(D)J recombinase limits the potential genomic damage that could otherwise result from RAG-mediated DNA cleavage. ..
- Veiga P, Gallini C, Beal C, Michaud M, Delaney M, DuBois A, et al. Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes. Proc Natl Acad Sci U S A. 2010;107:18132-7 pubmed publisher..Here, we show that colitis improved in T-bet(-/-)Rag2(-/-) mice that consumed a fermented milk product containing Bifidobacterium animalis subsp...
- Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2010;463:540-4 pubmed publisher..Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'. ..
- Mombaerts P, Iacomini J, Johnson R, Herrup K, Tonegawa S, Papaioannou V. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68:869-77 pubmed..Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice. ..
- van den Broek M, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz W, et al. Decreased tumor surveillance in perforin-deficient mice. J Exp Med. 1996;184:1781-90 pubmed
- 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. ..
- Yu W, Nagaoka H, Jankovic M, Misulovin Z, Suh H, Rolink A, et al. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization. Nature. 1999;400:682-7 pubmed..mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen...
- Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248:1517-23 pubmed..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction. ..
- Shinkai Y, Alt F. CD3 epsilon-mediated signals rescue the development of CD4+CD8+ thymocytes in RAG-2-/- mice in the absence of TCR beta chain expression. Int Immunol. 1994;6:995-1001 pubmed..Together, these data strongly indicate that TCR beta chain-mediated developmental signals are transduced by CD3 components and provide potential insights into mechanisms by which TCR beta chain expression may effect this process. ..
- Mao C, Tili E, Dose M, Haks M, Bear S, Maroulakou I, et al. Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J Immunol. 2007;178:5443-53 pubmed..Akt1 and Akt2 also contribute to the differentiation process by promoting the survival of the DP thymocytes. ..
- Spanopoulou E, Cortes P, Shih C, Huang C, Silver D, Svec P, et al. Localization, interaction, and RNA binding properties of the V(D)J recombination-activating proteins RAG1 and RAG2. Immunity. 1995;3:715-26 pubmedThe RAG1 and RAG2 gene products are indispensable for activating somatic rearrangement of antigen receptor gene segments. The two proteins form a stable complex in primary thymocytes as well as when expressed in adherent cells...
- Sekiguchi J, Whitlow S, Alt F. Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs. Mol Cell. 2001;8:1383-90 pubmedRAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs...
- Borghesi L, Hsu L, Miller J, Anderson M, Herzenberg L, Herzenberg L, et al. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. J Exp Med. 2004;199:491-502 pubmed..Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP...
- Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J, Lanzavecchia A, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304:104-7 pubmed..Here we show that intrahepatic injection of CD34+ human cord blood cells into conditioned newborn Rag2-/-gammac-/- mice leads to de novo development of B, T, and dendritic cells; formation of structured primary and ..
- Corneo B, Wendland R, Deriano L, Cui X, Klein I, Wong S, et al. Rag mutations reveal robust alternative end joining. Nature. 2007;449:483-6 pubmed..mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient...
- Takenaka K, Prasolava T, Wang J, Mortin Toth S, Khalouei S, Gan O, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8:1313-23 pubmed..Thus, we have identified Sirpa polymorphism as a potent genetic determinant of the engraftment of human hematopoietic stem cells. ..
- Le Dévédec S, van Roosmalen W, Maria N, Grimbergen M, Pont C, Lalai R, et al. An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2(-/-) gammac (-/-) mouse. Clin Exp Metastasis. 2009;26:673-84 pubmed publisher..Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2(-/-)gammac(-/-) mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland...
- Tsukamoto H, Irie A, Senju S, Hatzopoulos A, Wojnowski L, Nishimura Y. B-Raf-mediated signaling pathway regulates T cell development. Eur J Immunol. 2008;38:518-27 pubmed publisher..In conclusion, we present first evidence for the important role of B-Raf-mediated signaling in T cell development. ..
- Guidos C, Williams C, Grandal I, Knowles G, Huang M, Danska J. V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors. Genes Dev. 1996;10:2038-54 pubmed..These results demonstrate that a p53-mediated DNA damage checkpoint contributes to the immune deficiency characteristic of the scid mutation and limits the oncogenic potential of DSBs generated during V(D)J recombination. ..
- Maggio Price L, Treuting P, Bielefeldt Ohmann H, Seamons A, Drivdahl R, Zeng W, et al. Bacterial infection of Smad3/Rag2 double-null mice with transforming growth factor-beta dysregulation as a model for studying inflammation-associated colon cancer. Am J Pathol. 2009;174:317-29 pubmed publisher..to increased cancer susceptibility, we crossed Smad3-null mice with mice deficient in both B and T lymphocytes (Rag2(-/-) mice)...
- Werneck M, Lugo Villarino G, Hwang E, Cantor H, Glimcher L. T-bet plays a key role in NK-mediated control of melanoma metastatic disease. J Immunol. 2008;180:8004-10 pubmed..Taken together, these results show for the first time an irreplaceable role for T-bet in the NK-mediated cross-talk between innate and adaptive immune responses to metastatic disease. ..
- Neiditch M, Lee G, Huye L, Brandt V, Roth D. The V(D)J recombinase efficiently cleaves and transposes signal joints. Mol Cell. 2002;9:871-8 pubmed
- Lu L, Kim H, Werneck M, Cantor H. Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc Natl Acad Sci U S A. 2008;105:19420-5 pubmed publisher..Further analysis revealed that genetic disruption of the Qa-1-CD94/NKG2A interaction unleashes robust CD8 Treg cell activity that completely abolishes development of EAE. ..
- Hagenbeek T, Naspetti M, Malergue F, Garcon F, Nunes J, Cleutjens K, et al. The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and Pre-TCR-mediated signaling. J Exp Med. 2004;200:883-94 pubmed..Analysis of mice deficient for Pten and CD3gamma; Pten and gammac; or Pten, gammac, and Rag2 revealed that deletion of PTEN can substitute for both IL-7 and pre-TCR signals...
- Garrett W, Lord G, Punit S, Lugo Villarino G, Mazmanian S, Ito S, et al. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell. 2007;131:33-45 pubmed..These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD. ..
- Ott R, Simma O, Kollmann K, Weisz E, Zebedin E, Schorpp Kistner M, et al. JunB is a gatekeeper for B-lymphoid leukemia. Oncogene. 2007;26:4863-71 pubmed..Similarly, bcr/abl p185-transformed JunB-deficient (junB(Delta/Delta)) cells induced leukemia in RAG2(-/-) mice displaying a more malignant phenotype...
- Zhu C, Mills K, Ferguson D, Lee C, Manis J, Fleming J, et al. Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell. 2002;109:811-21 pubmed..This recombination event employs a microhomology-based end-joining repair pathway, as opposed to classic NHEJ or homologous recombination. These findings suggest a general model for oncogenic complicon formation. ..
- Wayne J, Suh H, Misulovin Z, Sokol K, Inaba K, Nussenzweig M. A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell development. Immunity. 1994;1:95-107 pubmed..We propose that in addition to a previously documented role in V(D)J recombination, RAG-1 and RAG-2 expression must be properly regulated for completion of normal T cell development ..
- Colucci F, Soudais C, Rosmaraki E, Vanes L, Tybulewicz V, Di Santo J. Dissecting NK cell development using a novel alymphoid mouse model: investigating the role of the c-abl proto-oncogene in murine NK cell differentiation. J Immunol. 1999;162:2761-5 pubmed..activating gene (RAG)-2 mutant mice, we have generated a novel alymphoid (B-, T-, and NK-) mouse strain (RAG2/gammac) suitable for NK complementation in vivo...
- Liang H, Hsu L, Cado D, Cowell L, Kelsoe G, Schlissel M. The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development. Immunity. 2002;17:639-51 pubmedPrevious in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice...
- Lin W, Desiderio S. Cell cycle regulation of V(D)J recombination-activating protein RAG-2. Proc Natl Acad Sci U S A. 1994;91:2733-7 pubmed..The variation in RAG-2 protein is likely to be established, at least in part, by a posttranscriptional mechanism. These observations suggest that V(D)J rearrangement occurs entirely or preferentially within G0/G1. ..
- Lazarevic V, Zullo A, Schweitzer M, Staton T, Gallo E, Crabtree G, et al. The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells. Nat Immunol. 2009;10:306-13 pubmed publisher..We found that Egr2 was important in the selection, survival and maturation of NKT cells. Our findings emphasize the importance of the calcineurin-NFAT-Egr2 pathway in the development of the NKT lymphocyte lineage. ..
- Schatz D, Oettinger M, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989;59:1035-48 pubmed..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself. ..
- Williams J, Hathcock K, Klug D, Harada Y, Choudhury B, Allison J, et al. Regulated costimulation in the thymus is critical for T cell development: dysregulated CD28 costimulation can bypass the pre-TCR checkpoint. J Immunol. 2005;175:4199-207 pubmed
- Callen E, Bunting S, Huang C, Difilippantonio M, Wong N, Khor B, et al. Chimeric IgH-TCRalpha/delta translocations in T lymphocytes mediated by RAG. Cell Cycle. 2009;8:2408-12 pubmed..We suggest a new model for how oncogenic translocations can arise from two non-concerted physiological DSBs...
- Cuomo C, Oettinger M. Analysis of regions of RAG-2 important for V(D)J recombination. Nucleic Acids Res. 1994;22:1810-4 pubmed..In contrast, all mutations we created in the N-terminal region severely decreased recombination. Thus, the core active region required for V(D)J recombination is confined to the first three-quarters of the RAG-2 protein. ..
- Chen J, Ma A, Young F, Alt F. IL-2 receptor alpha chain expression during early B lymphocyte differentiation. Int Immunol. 1994;6:1265-8 pubmed..Its potential function in early B cell differentiation is discussed in comparison with its role in thymocyte differentiation. ..
- Mullin M, Lightfoot K, Clarke R, Miller M, Lahesmaa R, Cantrell D. The RhoA transcriptional program in pre-T cells. FEBS Lett. 2007;581:4309-17 pubmed..causes a developmental block that pheno-copies the consequence of losing pre-TCR expression in Recombinase gene 2 (Rag2) null mice...
- Shinkai Y, Koyasu S, Nakayama K, Murphy K, Loh D, Reinherz E, et al. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science. 1993;259:822-5 pubmed..RAG-2-/- mice that expressed alpha and beta TCR transgenes developed both DP and single positive thymocytes. Thus, the TCR beta subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition. ..
- Shinkai Y, Rathbun G, Lam K, Oltz E, Stewart V, Mendelsohn M, et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992;68:855-67 pubmed..Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes. ..
- Akamatsu Y, Monroe R, Dudley D, Elkin S, Gartner F, Talukder S, et al. Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice. Proc Natl Acad Sci U S A. 2003;100:1209-14 pubmedThe recombination-activating gene (RAG)1 and RAG2 proteins comprise the lymphocyte-specific components of the V(D)J recombinase and are required for the assembly of antigen-receptor variable-region genes...
- Hsu L, Lauring J, Liang H, Greenbaum S, Cado D, Zhuang Y, et al. A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity. 2003;19:105-17 pubmedAlthough expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood...
- Anderson C, Oukka M, Kuchroo V, Sacks D. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med. 2007;204:285-97 pubmed
- Lu L, Ikizawa K, Hu D, Werneck M, Wucherpfennig K, Cantor H. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity. 2007;26:593-604 pubmed
- Curry J, Schlissel M. RAG2's non-core domain contributes to the ordered regulation of V(D)J recombination. Nucleic Acids Res. 2008;36:5750-62 pubmed publisher..In mice lacking the non-core domain of RAG2 the ordered rearrangement is disturbed and direct V to D rearrangements are 10- to 1000-times increased in tri-..
- Cebrat M, Cebula A, Laszkiewicz A, Kasztura M, Miazek A, Kisielow P. Mechanism of lymphocyte-specific inactivation of RAG-2 intragenic promoter of NWC: implications for epigenetic control of RAG locus. Mol Immunol. 2008;45:2297-306 pubmed publisher..The implications of our findings for understanding mechanisms regulating transcription within RAG/NWC locus in different cells are discussed and the model of epigenetic control of this locus is proposed. ..
- von Freeden Jeffry U, Solvason N, Howard M, Murray R. The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity. 1997;7:147-54 pubmed..These data specify a T cell lineage developmental transition point, prior to T cell antigen receptor rearrangement, where IL-7 signal transduction is linked to an anti-apoptosis mechanism and the cell cycle. ..
- Erdman S, Rao V, Poutahidis T, Ihrig M, Ge Z, Feng Y, et al. CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res. 2003;63:6042-50 pubmed..Regulatory lymphocytes and cytokines may have implications for novel therapies for colon cancer in humans...