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Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice.

http://www.ncbi.nlm.nih.gov/pubmed/15199411

Deregulated expression of both Myc and Bcl-X(L) are consistent features of human plasma cell neoplasms (PCNs). To investigate whether targeted expression of Myc and Bcl-X(L) in mouse plasma cells might lead to an improved model of human PCN, we generated Myc transgenics by inserting a single-copy histidine-tagged mouse Myc gene, Myc(His), into the mouse Ig heavy-chain Calpha locus. We also generated Bcl-X(L) transgenic mice that contain a multicopy Flag-tagged mouse Bcl-x(Flag) transgene driven by the mouse Ig kappa light-chain 3' enhancer. Single-transgenic Bcl-X(L) mice remained tumor free by 380 days of age, whereas single-transgenic Myc mice developed B cell tumors infrequently (4 of 43, 9.3%). In contrast, double-transgenic Myc/Bcl-X(L) mice developed plasma cell tumors with short onset (135 days on average) and full penetrance (100% tumor incidence). These tumors produced monoclonal Ig, infiltrated the bone marrow, and contained elevated amounts of Myc(His) and Bcl-X(L)(Flag) proteins compared with the plasma cells that accumulated in large numbers in young tumor-free Myc/Bcl-X(L) mice. Our findings demonstrate that the enforced expression of Myc and Bcl-X(L) by Ig enhancers with peak activity in plasma cells generates a mouse model of human PCN that recapitulates some features of human multiple myeloma.

Pubmed ID: 15199411 RIS Download

Mesh terms: Animals | Antibodies, Monoclonal | Bone Marrow | Gene Expression Regulation, Neoplastic | Humans | Lymph Nodes | Mice | Mice, Inbred C57BL | Mice, Transgenic | Plasmacytoma | Proto-Oncogene Proteins c-bcl-2 | Proto-Oncogene Proteins c-myc | Spleen | bcl-X Protein

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Associated grants

  • Agency: NCI NIH HHS, Id: T32 CA09138-27

Mouse Genome Informatics (Data, Gene Annotation)

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