title: T cell tumorigenesis in Lmo2 transgenic mice is independent of V-D-J recombinase activity.
abstract: The LMO2 gene is involved in T-cell acute leukaemia (T-ALL) in children with chromosomal translocations t(11;14)(p13;q11) or (7;11)(q35;p13). Transgenic expression of Lmo2 in T cells results in clonal tumours with long latency indicating that mutations in other genes are required for the development of overt tumours. RAG V-D-J recombinase can mediate genetic transposition and thus might create the secondary mutations necessary for T-ALL. Tumour development was compared in Lmo2 transgenic mice in the presence or absence of the Rag1 gene. No difference was observed in the rate of tumour formation nor in tumour histology in Lmo2-transgenic mice with or without Rag1. We conclude that, in this model, RAG recombinase is not a major mediator of mutations needed for T cell tumorigenesis and that antigen binding to alpha-beta or to gamma-delta T cell receptor does not play a role in tumorigenesis. The driving force behind the mutational process involved in this transgenic model remains obscure.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
authors.forename: L F
authors.initials: LF
authors.lastname: Drynan
authors.forename: T L
authors.initials: TL
authors.lastname: Hamilton
authors.forename: T H
authors.initials: TH
authors.lastname: Rabbitts
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008667:Metalloproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D013945:Thymoma / Q000209:etiology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; C064658:RAG-1 protein