Lymphopoiesis in transgenic mice over-expressing Artemis

Gene Ther. 2016 Feb;23(2):176-86. doi: 10.1038/gt.2015.95. Epub 2015 Oct 1.


Artemis is a factor of the non-homologous end joining pathway involved in DNA double-strand break repair that has a critical role in V(D)J recombination. Mutations in DCLRE1C/ARTEMIS gene result in radiosensitive severe combined immunodeficiency in humans owing to a lack of mature T and B cells. Given the known drawbacks of allogeneic hematopoietic stem cell transplantation (HSCT), gene therapy appears as a promising alternative for these patients. However, the safety of an unregulated expression of Artemis has to be established. We developed a transgenic mouse model expressing human Artemis under the control of the strong CMV early enhancer/chicken beta actin promoter through knock-in at the ROSA26 locus to analyze this issue. Transgenic mice present a normal development, maturation and function of T and B cells with no signs of lymphopoietic malignancies for up to 15 months. These results suggest that the over-expression of Artemis in mice (up to 40 times) has no deleterious effects in early and mature lymphoid cells and support the safety of gene therapy as a possible curative treatment for Artemis-deficient patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA-Binding Proteins
  • Endonucleases / genetics*
  • Endonucleases / therapeutic use
  • Genetic Therapy
  • Humans
  • Immunoglobulin Class Switching / genetics
  • Lymphopoiesis* / genetics
  • Mice
  • Mice, Transgenic
  • Severe Combined Immunodeficiency / therapy
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology


  • DNA-Binding Proteins
  • DCLRE1C protein, human
  • Endonucleases