Previous Article | Next Article 
Molecular and Cellular Biology, December 1999, p. 8240-8253, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Massive Apoptosis of Thymocytes in
T-Cell-Deficient Id1 Transgenic Mice
Dongsoo
Kim,
Xiao-Cong
Peng, and
Xiao-Hong
Sun*
Department of Cell Biology, Kaplan Cancer
Center, New York University School of Medicine, New York, New York
10016
Received 5 February 1999/Returned for modification 23 March
1999/Accepted 23 August 1999
Id1 is an inhibitor of a group of basic helix-loop-helix
transcription factors, collectively called E proteins, which includes E12, E47, E2-2, and HEB. We have generated transgenic mice in which Id1
is specifically expressed in T cells. The total number of thymocytes in
these mice is less than 4% of that in wild-type mice. The majority of
the transgenic thymocytes are CD4 and CD8 double negative and bear the
cell surface markers of multipotent progenitor cells. A small number of
thymocytes, however, differentiate into CD4 or CD8 single-positive T
cells, which also display different characteristics from their
wild-type counterparts. More importantly, apoptotic cells constitute
about 50% of the total thymocytes. These apoptotic thymocytes have
rearranged their T-cell receptor genes, suggesting that they are
differentiating T cells. This finding has raised the possibility that
the T-cell deficiency in Id1 transgenic mice is the result of a massive
apoptosis of differentiating T cells triggered by Id1 expression as
opposed to a developmental block at the earliest progenitor stage. The progenitor cells accumulated in the transgenic mice might have survived
because they are not susceptible to the apoptotic signals. Despite the
massive cell death of the thymocytes at young ages, Id1 transgenic mice
frequently develop T-cell lymphoma later in their life span, and
lymphomagenesis appears to occur at different stages of T-cell
development. Taken together, our data suggest that E proteins, being
the targets of Id1, are essential regulators for normal T-cell
differentiation and tumor suppression.
*
Corresponding author. Present address: Oklahoma Medical
Research Foundation, 825 Northeast 13th St., Oklahoma City, OK 73104. Phone: (405) 271-2864. Fax: (405) 271-7128. E-mail:
XH-Sun{at}omrf.ouhsc.edu.
Molecular and Cellular Biology, December 1999, p. 8240-8253, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Wang, H.-C., Perry, S. S., Sun, X.-H.
(2009). Id1 Attenuates Notch Signaling and Impairs T-Cell Commitment by Elevating Deltex1 Expression. Mol. Cell. Biol.
29: 4640-4652
[Abstract]
[Full Text]
-
Ji, M., Li, H., Suh, H. C., Klarmann, K. D., Yokota, Y., Keller, J. R.
(2008). Id2 intrinsically regulates lymphoid and erythroid development via interaction with different target proteins. Blood
112: 1068-1077
[Abstract]
[Full Text]
-
Swarbrick, A., Roy, E., Allen, T., Bishop, J. M.
(2008). Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response. Proc. Natl. Acad. Sci. USA
105: 5402-5407
[Abstract]
[Full Text]
-
Nie, L., Perry, S. S., Zhao, Y., Huang, J., Kincade, P. W., Farrar, M. A., Sun, X.-H.
(2008). Regulation of Lymphocyte Development by Cell-Type-Specific Interpretation of Notch Signals. Mol. Cell. Biol.
28: 2078-2090
[Abstract]
[Full Text]
-
Perry, S. S., Zhao, Y., Nie, L., Cochrane, S. W., Huang, Z., Sun, X.-H.
(2007). Id1, but not Id3, directs long-term repopulating hematopoietic stem-cell maintenance. Blood
110: 2351-2360
[Abstract]
[Full Text]
-
Wojciechowski, J., Lai, A., Kondo, M., Zhuang, Y.
(2007). E2A and HEB Are Required to Block Thymocyte Proliferation Prior to Pre-TCR Expression. J. Immunol.
178: 5717-5726
[Abstract]
[Full Text]
-
Birkenkamp, K. U., Essafi, A., van der Vos, K. E., da Costa, M., Hui, R. C.-Y., Holstege, F., Koenderman, L., Lam, E. W.-F., Coffer, P. J.
(2007). FOXO3a Induces Differentiation of Bcr-Abl-transformed Cells through Transcriptional Down-regulation of Id1. J. Biol. Chem.
282: 2211-2220
[Abstract]
[Full Text]
-
Wencker, M., Sausse, C., Derse, D., Gazzolo, L., Duc Dodon, M.
(2007). Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes. J. Virol.
81: 301-308
[Abstract]
[Full Text]
-
Yang, Y., Liou, H.-C., Sun, X.-H.
(2006). Id1 Potentiates NF-{kappa}B Activation upon T Cell Receptor Signaling. J. Biol. Chem.
281: 34989-34996
[Abstract]
[Full Text]
-
Lazorchak, A. S., Wojciechowski, J., Dai, M., Zhuang, Y.
(2006). E2A Promotes the Survival of Precursor and Mature B Lymphocytes. J. Immunol.
177: 2495-2504
[Abstract]
[Full Text]
-
Leeanansaksiri, W., Wang, H., Gooya, J. M., Renn, K., Abshari, M., Tsai, S., Keller, J. R.
(2005). IL-3 Induces Inhibitor of DNA-Binding Protein-1 in Hemopoietic Progenitor Cells and Promotes Myeloid Cell Development. J. Immunol.
174: 7014-7021
[Abstract]
[Full Text]
-
Huang, Z., Nie, L., Xu, M., Sun, X.-H.
(2004). Notch-Induced E2A Degradation Requires CHIP and Hsc70 as Novel Facilitators of Ubiquitination. Mol. Cell. Biol.
24: 8951-8962
[Abstract]
[Full Text]
-
Qi, Z., Sun, X.-H.
(2004). Hyperresponse to T-Cell Receptor Signaling and Apoptosis of Id1 Transgenic Thymocytes. Mol. Cell. Biol.
24: 7313-7323
[Abstract]
[Full Text]
-
Hata, K., Yoshimoto, T., Mizuguchi, J.
(2004). CD40 Ligand Rescues Inhibitor of Differentiation 3-Mediated G1 Arrest Induced by Anti-IgM in WEHI-231 B Lymphoma Cells. J. Immunol.
173: 2453-2461
[Abstract]
[Full Text]
-
Ferrando, A. A., Armstrong, S. A., Neuberg, D. S., Sallan, S. E., Silverman, L. B., Korsmeyer, S. J., Look, A. T.
(2003). Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood
102: 262-268
[Abstract]
[Full Text]
-
Herblot, S., Aplan, P. D., Hoang, T.
(2002). Gradient of E2A Activity in B-Cell Development. Mol. Cell. Biol.
22: 886-900
[Abstract]
[Full Text]
-
Ueda, E., Kurebayashi, S., Sakaue, M., Backlund, M., Koller, B., Jetten, A. M.
(2002). High Incidence of T-Cell Lymphomas in Mice Deficient in the Retinoid-related Orphan Receptor ROR{gamma}. Cancer Res.
62: 901-909
[Abstract]
[Full Text]
-
Wilson, J. W., Deed, R. W., Inoue, T., Balzi, M., Becciolini, A., Faraoni, P., Potten, C. S., Norton, J. D.
(2001). Expression of Id Helix-Loop-Helix Proteins in Colorectal Adenocarcinoma Correlates with p53 Expression and Mitotic Index. Cancer Res.
61: 8803-8810
[Abstract]
[Full Text]
-
Takeuchi, A., Yamasaki, S., Takase, K., Nakatsu, F., Arase, H., Onodera, M., Saito, T.
(2001). E2A and HEB Activate the Pre-TCR{alpha} Promoter During Immature T Cell Development. J. Immunol.
167: 2157-2163
[Abstract]
[Full Text]
-
Barndt, R. J., Dai, M., Zhuang, Y.
(2000). Functions of E2A-HEB Heterodimers in T-Cell Development Revealed by a Dominant Negative Mutation of HEB. Mol. Cell. Biol.
20: 6677-6685
[Abstract]
[Full Text]
-
Wang, J., Jani-Sait, S. N., Escalon, E. A., Carroll, A. J., de Jong, P. J., Kirsch, I. R., Aplan, P. D.
(2000). The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene. Proc. Natl. Acad. Sci. USA
97: 3497-3502
[Abstract]
[Full Text]
-
Huang, S., Brandt, S. J.
(2000). mSin3A Regulates Murine Erythroleukemia Cell Differentiation through Association with the TAL1 (or SCL) Transcription Factor. Mol. Cell. Biol.
20: 2248-2259
[Abstract]
[Full Text]
-
Norton, J.
(2000). ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J. Cell Sci.
113: 3897-3905
[Abstract]
-
Ikawa, T., Fujimoto, S., Kawamoto, H., Katsura, Y., Yokota, Y.
(2001). Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc. Natl. Acad. Sci. USA
98: 5164-5169
[Abstract]
[Full Text]