VDJ recombination
Asarnow, D. M., Cado, D., and Raulet, D. H. (1993). Selection is not required to produce invariant T-cell receptor gamma-gene junctional sequences. Nature 362, 158-160.
Zhang, Y., Cado, D., Asarnow, D. M., Komori, T., Alt, F. W., Raulet, D. H., and Allison, J. P. (1995). The role of short homology repeats and TdT in generation of the invariant gamma delta antigen receptor repertoire in the fetal thymus. Immunity 3, 439-447.
Kang, J., Coles, M., Cado, D., and Raulet, D. H. (1998). The developmental fate of T cells is critically influenced by TCRgammadelta expression. Immunity 8, 427-438.
Kang, J., Fehling, H. J., Laplace, C., Malissen, M., Cado, D., and Raulet, D. H. (1998). T cell receptor gamma gene regulatory sequences prevent the function of a novel TCRgamma/pTalpha pre-T cell receptor. Immunity 8, 713-721.
TCR gene regulation & B cell development
Diaz, P., Cado, D., and Winoto, A. (1994). A locus control region in the T cell receptor alpha/delta locus. Immunity 1, 207-217.
Ortiz, B. D., Cado, D., Chen, V., Diaz, P. W., and Winoto, A. (1997). Adjacent DNA elements dominantly restrict the ubiquitous activity of a novel chromatin-opening region to specific tissues. EMBO J. 16, 5037-5045.
Baker, J. E., Cado, D., and Raulet, D. H. (1998). Developmentally programmed rearrangement of T cell receptor Vgamma genes is controlled by sequences immediately upstream of the Vgamma genes. Immunity 9, 159-168.
Baker, J. E., Kang, J., Xiong, N., Chen, T., Cado, D., and Raulet, D. H. (1999). A novel element upstream of the Vgamma2 gene in the murine T cell receptor gamma locus cooperates with the 3' enhancer to act as a locus control region. J. Exp. Med. 190, 669-679.
Ortiz, B. D., Cado, D., and Winoto, A. (1999). A new element within the T-cell receptor alpha locus required for tissue-specific locus control region activity. Mol. Cell Biol. 19, 1901-1909.
Ortiz, B. D., Harrow, F., Cado, D., Santoso, B., and Winoto, A. (2001). Function and factor interactions of a locus control region element in the mouse t cell receptor-alpha/dad1 gene locus. J. Immunol. 167, 3836-3845.
Tanamachi, D. M., Moniot, D. C., Cado, D., Liu, S. D., Hsia, J. K., and Raulet, D. H. (2004). Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and identification of a critical regulatory element. J. Immunol. 172, 1074-1082.
Hsu, L. Y., Liang, H. E., Johnson, K., Kang, C., and Schlissel, M. S. (2004). Pax5 Activates Immunoglobulin Heavy Chain V to DJ Rearrangement in Transgenic Thymocytes. J. Exp. Med. 199, 825-830.
Xiong, N., Baker, J. E., Kang, C., and Raulet, D. H. (2004). The genomic arrangement of T cell receptor variable genes is a determinant of the developmental rearrangement pattern. Proc. Natl. Acad. Sci. USA 101, 260-265.
Xiong, N., Kang, C., and Raulet, D. H. (2004). Positive selection of dendritic epidermal gammadelta T cell precursors in the fetal thymus determines expression of skin-homing receptors. Immunity 21, 121-131.
Apoptosis
Calnan, B., Szychowski, S., Chan, F. K. M., Cado, D., and Winoto, A. (1995). A role of the orphan steroid receptor Nur77 in antigen-induced negative selection. Immunity 3, 273-282.
Cheng, L. E., Chan, F. K., Cado, D., and Winoto, A. (1997). Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T cell apoptosis. EMBO J. 16, 1865-1875.
Hong, N. A., Kabra, N. H., Hsieh, S. N., Cado, D., and Winoto, A. (1999). In vivo overexpression of Dad1, the defender against apoptotic death-1, enhances T cell proliferation but does not protect against apoptosis. J. Immunol. 163, 1888-1893.
Kabra, N. H., Cado, D., and Winoto, A. (1999). A Tailless Fas-FADD Death-Effector Domain Chimera is Sufficient to Execute Fas Function in T cells but Not B cells of MRL-lpr/lpr Mice. J. Immunol. 162, 2766-2774.
Kuang, A. A., Cado, D., and Winoto, A. (1999). Nur77 transcription activity correlates with its in vivo apoptotic function. Eur. J. Immunol. 11, 3722-3728.
Kabra, N. H., Kang, C., Hsing, L. C., Zhang, J., and Winoto, A. (2001). T cell-specific FADD-deficient mice: FADD is required for early T cell development. Proc. Natl. Acad. Sci. USA 98, 6307-6312.
Rajpal, A., Cho, Y. A., Yelent, B., Koza-Taylor, P. H., Li, D., Chen, E., Whang, M., Kang, C., Turi, T. G., and Winoto, A. (2003). Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J. 22, 6526-6536.
Hua, Z. C., Sohn, S. J., Kang, C., Cado, D., and Winoto, A. (2003). A Function of Fas-Associated Death Domain Protein in Cell Cycle Progression Localized to a Single Amino Acid at Its C-Terminal Region. Immunity 18, 513-521.
NK cells
Held, W., Cado, D., and Raulet, D. H. (1996). Transgenic expression of the Ly49A natural killer cell receptor confers class I major histocompatibility complex (MHC)-specific inhibition and prevents bone marrow allograft rejection. J. Exp. Med. 184, 2037-2041.
Hanke, T., Takizawa, H., McMahon, C. W., Busch, D. H., Pamer, E. G., Miller, J. D., Altman, J. D., Liu, Y., Cado, D., Lemonnier, F. A., et al. (1999). Direct assessment of MHC class I binding by seven Ly49 inhibitory NK cell receptors. Immunity 11, 67-77.
Corral, L., Hanke, T., Vance, R. E., Cado, D., and Raulet, D. H. (2000). NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules. Eur. J. Immunol. 30, 920-930.
Vance, R. E., Jamieson, A. M., Cado, D., and Raulet, D. H. (2002). Implications of CD94 deficiency and monoallelic NKG2A expression for natural killer cell development and repertoire formation. Proc. Natl. Acad. Sci. USA 99, 868-873.
Signaling in T cell development
Itano, A., Cado, D., Chan, F. K., and Robey, E. (1994). A role for the cytoplasmic tail of the beta chain of CD8 in thymic selection. Immunity 1, 287-290.
Robey, E., Chang, D., Itano, A., Cado, D., Alexander, H., Lans, D., Weinmaster, G., and Salmon, P. (1996). An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 87, 483-492.
Washburn, T., Schweighoffer, E., Gridley, T., Chang, D., Fowlkes, B. J., Cado, D., and Robey, E. (1997). Notch activity influences the alphabeta versus gammadelta T cell lineage decision. Cell 88, 833-843.
Salmon, P., Mong, M., Kang, X. J., Cado, D., and Robey, E. (1999). The role of CD8 alpha' in the CD4 versus CD8 lineage choice. J. Immunol. 163, 5312-5318.
Adipocyte biology
Kim, K. H., Zhao, L., Moon, Y., Kang, C., and Sul, H. S. (2004). Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc. Natl. Acad. Sci. USA 101, 6780-6785.
Latasa, M. J., Griffin, M. J., Moon, Y. S., Kang, C., and Sul, H. S. (2003). Occupancy and function of the -150 sterol regulatory element and -65 E-box in nutritional regulation of the fatty acid synthase gene in living animals. Mol. Cell Biol. 23, 5896-5907.
Lee, K., Villena, J. A., Moon, Y. S., Kim, K. H., Lee, S., Kang, C., and Sul, H. S. (2003). Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). J. Clin. Invest. 111, 453-461.
Antigen Processing
Schwab, S. R., Li, K. C., Kang, C., and Shastri, N. (2003). Constitutive display of cryptic translation products by MHC class I molecules. Science 301, 1367-1371.
We have also generated many gene-targeted mice. These include:
Mice with deletion of the TCR locus control region
Hong, N., Cado, D., Mitchell, J., Ortiz, B. D., Hsieh, S. N., and Winoto, A. (1997). A targeted mutation at the T cell receptor alpha/delta locus impairs T cell development and reveals the presence of the nearby anti-apoptosis gene Dad1. Mol. Cell Biol. 17, 2151-2157.
CTLA-4 deficient mice
Chambers, C. A., Cado, D., Truong, T., and Allison, J. P. (1997). Thymocyte development is normal in CTLA-4-deficient mice. Proc. Natl. Acad. Sci. USA 94, 9296-9301.
FADD-/-and FADD-/-® RAG1-/- miceZhang, J., Cado, D., Chen, A., Kabra, N. H., and Winoto, A. (1998). Absence of Fas-mediated apoptosis and T cell receptor-induced proliferation in FADD-deficient mice. Nature 392, 296-300.
Zhang, J., Kabra, N. H., Cado, D., Kang, C., and Winoto, A. (2001). FADD-deficient T cells
exhibit a disaccord in regulation of the cell cycle machinery. J. Biol. Chem. 276, 29815-29818.
Dad1(Defender against apoptotic death) deficient mice
Hong, N. A., Flannery, M., Hsieh, S. N., Cado, D., Pedersen, R., and Winoto, A. (2000). Mice lacking Dad1, the defender against apoptotic death-1, express abnormal N-linked glycoproteins and undergo increased embryonic apoptosis. Dev. Biol. 220, 76-84.
Mice with deletion of the TCR gamma regulatory elements
Xiong, N., Kang, C., and Raulet, D. H. (2002). Redundant and unique roles of two enhancer elements in the TCRgamma locus in gene regulation and gammadelta T cell development. Immunity 16, 453-463.
Core RAG1 knock-in mice
Liang, H. E., Hsu, L. Y., Cado, D., Cowell, L. G., Kelsoe, G., and Schlissel, M. S. (2002). The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development. Immunity 17, 639-651.
MAP kinase ERK5-/- mice
Sohn, S. J., Sarvis, B. K., Cado, D., and Winoto, A. (2002). ERK5 MAPK Regulates Embryonic Angiogenesis and Acts as a Hypoxia-sensitive Repressor of Vascular Endothelial Growth Factor Expression. J. Biol. Chem. 277, 43344-43351.
Nor-1 orphan steroid receptor deficient mice
DeYoung, R. A., Baker, J. C., Cado, D., and Winoto, A. (2003). The orphan steroid receptor Nur77 family member Nor-1 is essential for early mouse embryogenesis. J. Biol. Chem. 278, 47104-47109.
Mice with deletion of a RAG enhancer element
Hsu, L. Y., Lauring, J., Liang, H. E., Greenbaum, S., Cado, D., Zhuang, Y., and Schlissel, M. S. (2003). A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity 19, 105-117.
DNA repair gene DDB2 deficient mice
Itoh, T., Cado, D., Kamide, R., and Linn, S. (2004). DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen. Proc. Natl. Acad. Sci. USA 101, 2052-2057.
T cell specific survivin deficient mice
Xing, Z., Conway, E. M., Kang, C., and Winoto, A. (2004). Essential Role of Survivin, an Inhibitor of Apoptosis Protein, in T Cell Development, Maturation, and Homeostasis. J. Exp. Med. 199, 69-80.
GFP-Ig kappa knock-in mice
Liang, H. E., Hsu, L. Y., Cado, D., and Schlissel, M. S. (2004). Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression. Cell 118, 19-29.
TRAIL-R deficient mice
Diehl, G. E., Yue, H. H., Hsieh, K., Kuang, A. A., Ho, M., Morici, L., Lenz, L. L., Cado, D., Riley, L. W., and Winoto, A. (2004). TRAIL-R as a negative regulator of innate immune cell responses. Submitted.
