Sustained pre-TCR expression in Notch1IC-transgenic rats impairs T cell maturation and selection

J van den Brandt, SH Kwon, T Hunig… - The Journal of …, 2005 - journals.aai.org
J van den Brandt, SH Kwon, T Hunig, KG McPherson, HM Reichardt
The Journal of Immunology, 2005journals.aai.org
Notch1 is involved in directing cell fate decisions in a variety of developmental scenarios.
Extending previous experiments in mice, we generated transgenic rats expressing the
intracellular domain of Notch1 in the thymus. Importantly, this leads to sustained expression
of the pre-TCR throughout thymocyte development, accompanied by a reduction of αβTCR
complexes. In addition, re-expression of RAG-1 and RAG-2 in TCRβ+ cells is impaired, and
the Vα repertoire is altered. Consequently, thymocytes in transgenic rats do not undergo …
Abstract
Notch1 is involved in directing cell fate decisions in a variety of developmental scenarios. Extending previous experiments in mice, we generated transgenic rats expressing the intracellular domain of Notch1 in the thymus. Importantly, this leads to sustained expression of the pre-TCR throughout thymocyte development, accompanied by a reduction of αβTCR complexes. In addition, re-expression of RAG-1 and RAG-2 in TCRβ+ cells is impaired, and the Vα repertoire is altered. Consequently, thymocytes in transgenic rats do not undergo positive selection and largely fail to progress to the single positive stage. According to our model, the previously reported effects of Notch1 on the CD4/CD8 cell fate decision may be explained by a differential sensitivity of the two lineages toward altered TCR signaling.
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