Faculty Collaboration Database

Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. J Clin Invest 2004 Jun;113(12):1763-73

Date

06/17/2004

Pubmed ID

15199411

Pubmed Central ID

PMC420503

DOI

10.1172/JCI20369

Scopus ID

2-s2.0-3042806890 (requires institutional sign-in at Scopus site)   95 Citations

Abstract

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.

Author List

Cheung WC, Kim JS, Linden M, Peng L, Van Ness B, Polakiewicz RD, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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