a quantitative study of the mechanisms behind thymic atrophy in gαi2-deficient mice during colitis development定量研究背后的机制在gαi2-deficient小鼠胸腺萎缩结肠炎的发展.pdfVIP

A Quantitative Study of the Mechanisms behind Thymic Atrophy in Gai2-Deficient Mice during Colitis Development 1 2 ¨ 1 Kristina Elgbratt , Andreas Jansson , Elisabeth Hultgren-Hornquist * ¨ ¨ ¨ ¨ 1 School of Health and Medical Sciences, Orebro University, Orebro, Sweden, 2 Systems Biology Research Centre, University of Skovde, Skovde, Sweden Abstract Mice deficient for the G protein subunit Gai2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The Gai22/ 2 mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the Gai22/ 2 mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai22/ 2 mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the Gai22/ 2 SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4+ and CD8+ thymocytes divide to the same extent before they