Homozygous iMycCα transgenic mice as a model of plasma B-cell lymphomas

Abstract

The 3' regulatory region (3'RR) located downstream from the Cα gene is the conductor of transcription, accessibility, and remodeling of the IgH locus at mature B-cell stages. Convincing demonstrations of the essential contributions of the 3'RR in B-cell lymphomagenesis have been provided by mouse models which bring the oncogene c-Myc under the 3'RR transcriptional control. In this study, we developed a mouse model of CD138⁺ plasma B-cell lymphomas. If the KI of c-myc directly into Cα just 5' to the 3'RR in iMycCα mice produced B-cell lymphomas with low kinetics, we enforced c-myc production in iMycCα mice by the generation of homozygous c-myc transgenic mice. Our results show that homozygous iMycCα mice lead to a mouse model of plasma CD138⁺ B-cell lymphomas with interesting and wide transcriptomic similarities to human multiple myeloma and appropriated emergence kinetics that can be used to test new experimental therapeutic approaches.

Keywords:

• Lymphocytes
• the development of B lymphocytes
• lymphoid leukemia

Acknowledgments

Authors are ‘Equipe Labellisée LIGUE 2018.’ N.G. was supported by a grant from ‘Société Française d’Hématologie.’ H.I. and M.F. are supported by University of Limoges and ‘Région Nouvelle Aquitaine.’ We thank the GenoToul (Toulouse, France, get.genotoul.fr) for RNA seq experiments. We thank the animal facility of Limoges University (BISCEm US 42 INSERM/UMS 2015 CNRS) for mouse housing.

Author contributions

N.G., M.F., H.I., and E.D. contributed equally. Y.D and J.C-M designed research. N.G., H.I., M.F. and Y.D. performed research. E.D., M.F., and Y.D. analyzed mRNAseq data. C.O. performed western blot experiments. M.F., J.C-M, C.O., E.D., and Y.D. wrote the paper. Y.D. obtained grant supports.

Disclosure statement

The authors declare no competing interest.

Additional information

Funding

This work was supported by Ligue Contre le Cancer.