Reversible activation of c-Myc in thymocytes enhances positive selection and induces proliferation and apoptosis in vitro

Inflammatory Disease and Lymphomagenesis Caused by Deletion of the Myc Antagonist Mnt in T Cells

“…Indeed, this speculative model has parallels with models of Myc-driven tumorigenesis (29,36) and provides a possible link between the development of inflammatory disease and lymphomagenesis in lck-Cre-Mnt flox/flox mice. Interestingly, c-Myc has been implicated in both negative selection and positive selection and strong transient activation of c-Myc can, like loss of Mnt, deplete DP T cells in vivo (5,40,43). Although there is no direct evidence indicating that Myc-induced apoptosis is linked to the development of inflammatory disease in transgenic mice, there is evidence that links a bypass in negative selection to Myc-induced T-cell lymphomagenesis (5).…”

Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation

“…To test in vivo the notion that Myc and Mad1 compete functionally, we crossed our lck-Mad1 transgenic mice with mice expressing the 4-hydroxytamoxifen (4-OHT)-dependent c-MycER TM protein under the control of the proximal lck promoter. Both lck-Mad1 and lck-c-mycER TM transgenic mice possess similar copy numbers of their requisite transgene (data not shown and Rudolph et al, 2000).…”

“…The generation of lck-c-mycER TM transgenic mice is described elsewhere (Rudolph et al, 2000). H-Y-TCR transgenic mice (H-2 b/b ) were originally described by von Boehmer (1990).…”

A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis

“…c-Myc promotes thymocyte proliferation and can lead to tumorigenesis when ectopically expressed (27)(28)(29)(30). To decipher whether Mnt antagonizes the consequences of Myc overexpression, we used mice in which the c-Myc gene was "knocked in" to the ROSA-26 locus downstream from a LoxP-flanked transcription termination sequence (31) and used Lck-Cre for T-cell-specific Myc expression.…”