Gene Symbol: rag2
Description: recombination activating gene 2
Alias: rag-2, zgc:136743, V(D)J recombination-activating protein 2
Species: zebrafish

Top Publications

  1. Langenau D, Feng H, Berghmans S, Kanki J, Kutok J, Look A. Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2005;102:6068-73 pubmed
    We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization of the onset and spread of this disease...
  2. Chen J, Jette C, Kanki J, Aster J, Look A, Griffin J. NOTCH1-induced T-cell leukemia in transgenic zebrafish. Leukemia. 2007;21:462-71 pubmed
    ..The ability of this model to detect a strong interaction between NOTCH1 and bcl2 suggests that genetic modifier screens have a high likelihood of revealing other genes that can cooperate with NOTCH1 to induce T-ALL. ..
  3. Langenau D, Jette C, Berghmans S, Palomero T, Kanki J, Kutok J, et al. Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish. Blood. 2005;105:3278-85 pubmed
    ..8-fold increase in GFP-labeled B cells in the kidney marrow. Fluorescent microscopic analysis of living rag2-EGFP-bcl-2 transgenic fish showed that their thymocytes were resistant to irradiation- and dexamethasone-induced ..
  4. Smith A, Raimondi A, Salthouse C, Ignatius M, Blackburn J, Mizgirev I, et al. High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia. Blood. 2010;115:3296-303 pubmed publisher
    ..Our experiments highlight the large numbers of zebrafish that can be experimentally assessed by cell transplantation and establish new high-throughput methods to functionally interrogate gene pathways involved in cancer self-renewal. ..
  5. Langenau D, Keefe M, Storer N, Guyon J, Kutok J, Le X, et al. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev. 2007;21:1382-95 pubmed
    ..When coupled with gene expression studies of this cell population, we propose that the zebrafish RMS cancer stem cell shares similar self-renewal programs as those found in activated satellite cells...
  6. Dong X, Zhang Z, Meng S, Pan C, Yang M, Wu X, et al. Parental exposure to bisphenol A and its analogs influences zebrafish offspring immunity. Sci Total Environ. 2018;610-611:291-297 pubmed publisher
  7. Hsu K, Traver D, Kutok J, Hagen A, Liu T, Paw B, et al. The pu.1 promoter drives myeloid gene expression in zebrafish. Blood. 2004;104:1291-7 pubmed
    ..These transgenic lines will be useful to dissect the cellular and molecular control of myeloid cell differentiation, and this promoter fragment may prove useful in the development of zebrafish models of acute myeloid leukemia. ..
  8. Liu X, Li Y, Shinton S, Rhodes J, Tang L, Feng H, et al. Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes. J Immunol. 2017;199:1706-1715 pubmed publisher
    ..Initiation of CD79:GFP expression in Rag2:mCherry+ cells and the timing of Ig H and L chain expression revealed simultaneous expression of both ..
  9. Moore J, Tang Q, Yordán N, Moore F, Garcia E, Lobbardi R, et al. Single-cell imaging of normal and malignant cell engraftment into optically clear prkdc-null SCID zebrafish. J Exp Med. 2016;213:2575-2589 pubmed
    ..Here, we characterize zebrafish with mutations in recombination activating gene 2 (rag2), DNA-dependent protein kinase (prkdc), and janus kinase 3 (jak3)...

More Information


  1. Langenau D, Zon L. The zebrafish: a new model of T-cell and thymic development. Nat Rev Immunol. 2005;5:307-17 pubmed
    ..Finally, we summarize the use of the zebrafish as a new model for assessing stem-cell function and for drug discovery. ..
  2. Blackburn J, Liu S, Raiser D, Martinez S, Feng H, Meeker N, et al. Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency. Leukemia. 2012;26:2069-78 pubmed publisher
    ..Taken together, these data indicate that a primary role of Notch signaling in T-ALL is to expand a population of pre-malignant thymocytes, of which a subset acquire the necessary mutations to become fully transformed LPCs. ..
  3. Tenente I, Hayes M, Ignatius M, McCarthy K, Yohe M, Sindiri S, et al. Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. elife. 2017;6: pubmed publisher
    ..Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth. ..
  4. Albacker C, Storer N, Langdon E, DiBiase A, Zhou Y, Langenau D, et al. The histone methyltransferase SUV39H1 suppresses embryonal rhabdomyosarcoma formation in zebrafish. PLoS ONE. 2013;8:e64969 pubmed publisher
    ..Gene expression profiling at these stages revealed that in the context of KRAS(G12D) overexpression, SUV39H1 may suppress cell cycle progression. Our studies provide evidence for the role of SUV39H1 as a tumor suppressor...
  5. Leacock S, Basse A, Chandler G, Kirk A, Rakheja D, Amatruda J. A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. Dis Model Mech. 2012;5:95-106 pubmed publisher
    ..These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene. ..
  6. Gutierrez A, Grebliunaite R, Feng H, Kozakewich E, Zhu S, Guo F, et al. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. J Exp Med. 2011;208:1595-603 pubmed publisher
    ..Our findings indicate that Akt pathway activation is sufficient for tumor maintenance in this model, even after loss of survival signals driven by the MYC oncogene. ..
  7. Wei Y, Xu J, Zhang W, Wen Z, Liu F. RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish. Development. 2016;143:2103-10 pubmed publisher
  8. Trede N, Ota T, Kawasaki H, Paw B, Katz T, Demarest B, et al. Zebrafish mutants with disrupted early T-cell and thymus development identified in early pressure screen. Dev Dyn. 2008;237:2575-84 pubmed publisher
    ..We discuss the advantage of this strategy and the general usefulness of the zebrafish as a model system for vertebrate lymphopoiesis and thymic organogenesis. ..
  9. Harrold I, Carbonneau S, Moore B, Nguyen G, Anderson N, Saini A, et al. Efficient transgenesis mediated by pigmentation rescue in zebrafish. Biotechniques. 2016;60:13-20 pubmed publisher
    ..Thus, this approach is ideal for generating transgenic fish for large-scale screens. ..
  10. Gutierrez A, Snyder E, Mariño Enríquez A, Zhang Y, Sioletic S, Kozakewich E, et al. Aberrant AKT activation drives well-differentiated liposarcoma. Proc Natl Acad Sci U S A. 2011;108:16386-91 pubmed publisher
    ..Our findings are unique in providing an animal model to decipher the molecular pathogenesis of WDLPS, and implicate AKT as a previously unexplored therapeutic target in this chemoresistant sarcoma...
  11. Hall C, Flores M, Chien A, Davidson A, Crosier K, Crosier P. Transgenic zebrafish reporter lines reveal conserved Toll-like receptor signaling potential in embryonic myeloid leukocytes and adult immune cell lineages. J Leukoc Biol. 2009;85:751-65 pubmed publisher
    ..These lines will provide a valuable resource for further resolving the contribution of MyD88 to early vertebrate immunity. ..
  12. Dooley K, Davidson A, Zon L. Zebrafish scl functions independently in hematopoietic and endothelial development. Dev Biol. 2005;277:522-36 pubmed
    ..Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development. ..
  13. Storer N, White R, Uong A, Price E, Nielsen G, Langenau D, et al. Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis. Development. 2013;140:3040-50 pubmed publisher
    ..Several zebrafish promoters were used, including the cdh15 and rag2 promoters, which drive gene expression in early muscle progenitors, and the mylz2 promoter, which is expressed in ..
  14. Sabaawy H, Azuma M, Embree L, Tsai H, Starost M, Hickstein D. TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2006;103:15166-71 pubmed
  15. Liau W, Tan S, Ngoc P, Wang C, Tergaonkar V, Feng H, et al. Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia. Leukemia. 2017;31:1798-1807 pubmed publisher
    ..Our results demonstrate that aberrant activation of the GIMAP enhancer contributes to T-cell leukemogenesis. ..
  16. Tsinkalovsky O, Vik Mo A, Ferreira S, Laerum O, Fjose A. Zebrafish kidney marrow contains ABCG2-dependent side population cells exhibiting hematopoietic stem cell properties. Differentiation. 2007;75:175-83 pubmed
    ..These rapid flow cytometric methods for purification of HSCs from zebrafish may greatly facilitate genetic analysis of stem cells using the advantages of this vertebrate model...
  17. Ru H, Chambers M, Fu T, Tong A, Liao M, Wu H. Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures. Cell. 2015;163:1138-1152 pubmed publisher
    ..The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 ..
  18. Zhong H, Li Z, Lin S, Chang Y. Initiation of V(D)J recombination in zebrafish (Danio rerio) ovaries. Mol Immunol. 2007;44:1784-92 pubmed
    ..Our data, therefore, substantiate the speculation that RAG might have been derived from a transposase, invading germ cells of ancient species, and later become a dedicated recombinase only expressed in developing lymphocytes. ..
  19. Pruitt M, Marin W, Waarts M, de Jong J. Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish. J Vis Exp. 2017;: pubmed publisher
    ..Furthermore, single-cell transcriptomics could be applied to identify the genetic features of these side population cells. ..
  20. Wei N, Pang W, Wang Y, Xiong Y, Xu R, Wu W, et al. Knockdown of PU.1 mRNA and AS lncRNA regulates expression of immune-related genes in zebrafish Danio rerio. Dev Comp Immunol. 2014;44:315-9 pubmed publisher
    ..1 AS shRNA for 2 days. Moreover, on day 0, 2 and 4, the levels of PU.1 and immune-related genes including TCRAC, Rag2, AID, IgLC-1, mIg, and sIg mRNAs were detected using real-time qPCR. The results showed that the levels of PU...
  21. Tang Q, Abdelfattah N, Blackburn J, Moore J, Martinez S, Moore F, et al. Optimized cell transplantation using adult rag2 mutant zebrafish. Nat Methods. 2014;11:821-4 pubmed publisher
    ..Here we have created rag2(E450fs) mutant zebrafish that have reduced numbers of functional T and B cells but are viable and fecund...
  22. Ma D, Wang L, Wang S, Gao Y, Wei Y, Liu F. Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish. Proc Natl Acad Sci U S A. 2012;109:21040-5 pubmed publisher
    ..Our results reveal that the foxn1-mcm2 axis plays a central role in the genetic regulatory network controlling thymus development in zebrafish...
  23. Moore J, Mulligan T, Torres Yordán N, Castranova D, Pham V, Tang Q, et al. T cell immune deficiency in zap70 mutant zebrafish. Mol Cell Biol. 2016;: pubmed
    ..zap70 mutant zebrafish show remarkable conservation of immune cell dysfunction as found in mice and humans and will serve as a valuable model to study zap70 immunodeficiency. ..
  24. Bertrand F, Olson S, Willett C, Wu G. Sequence of the rag1 and rag2 intergenic region in zebrafish (Danio rerio). Dev Immunol. 1998;5:211-4 pubmed
  25. Xu K, Liu H, Shi Z, Song G, Zhu X, Jiang Y, et al. Disruption of the RAG2 zinc finger motif impairs protein stability and causes immunodeficiency. Eur J Immunol. 2016;46:1011-9 pubmed publisher
    Although the RAG2 core domain is the minimal region required for V(D)J recombination, the noncore region also plays important roles in the regulation of recombination, and mutations in this region are often related to severe combined ..
  26. Silva A, Aw D, Palmer D. Evolutionary conservation of neuropeptide expression in the thymus of different species. Immunology. 2006;118:131-40 pubmed
    ..These findings suggest that neuropeptides may play an important role in T-cell development and provide further evidence of cross talk between the immune and neuroendocrine systems. ..
  27. Calcagnotto D, Schaefer S, DeSalle R. Relationships among characiform fishes inferred from analysis of nuclear and mitochondrial gene sequences. Mol Phylogenet Evol. 2005;36:135-53 pubmed
    ..aligned base pairs from the mitochondrial 16S and cytochrome b genes and the nuclear recombination activating gene (RAG2), seven in absentia (sia), forkhead (fkh), and alpha-tropomyosin (trop) gene loci confirmed the non-monophyly of ..
  28. Trede N, Zon L. Development of T-cells during fish embryogenesis. Dev Comp Immunol. 1998;22:253-63 pubmed