E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice.
Transgenic mice that contain the L-myc gene under the control of the immunoglobulin heavy-chain enhancer (E mu) express the transgene preferentially in T cells, develop thymic hyperplasia and are predisposed to T-cell lymphomas. An analogous E mu N-myc transgene is expressed preferentially in pre-B and B cells and provokes the development of B-cell neoplasias. Animals with an E mu pim-1 construct express the transgene in both B and T cells, but succumb to T-cell lymphomas. Complementation of the E mu N- and L-myc transgenic mice by breeding with E mu pim-1 animals leads to much more rapid development and a dramatically higher incidence of lymphoid malignancies, but the lineage specificity prescribed by the E mu N- and L-myc transgenes is maintained. The different oncogenic potential of myc genes is illustrated by the average latency period of tumor manifestation in double transgenics. Whereas c-myc/pim-1 animals develop pre-B-cell leukemia prenatally, the mean latency period for N-myc/pim-1 and L-myc/pim-1 mice is 36 and 94 days respectively. The N- and L-myc transgenes are expressed at high levels in tumors from double transgenic mice, but expression of the endogenous c- and N-myc genes is undetectable, directly implicating the myc transgenes in the tumor formation process.
Möröy
T
T
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Verbeek
S
S
Ma
A
A
Achacoso
P
P
Berns
A
A
Alt
F
F
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016259:Genes, myc / Q000502:physiology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D051573:Proto-Oncogene Proteins c-pim-1; D014158:Transcription, Genetic
D007145:Immunoglobulin kappa-Chains; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1