Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice.
Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.
Canela
Andrés
A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain.
Martín-Caballero
Juan
J
Flores
Juana M
JM
Blasco
María A
MA
D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D015870:Gene Expression; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019098:Telomerase; C509187:Tert protein, mouse