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Article Dans Une Revue Gene Ther Année : 2016

Lymphopoiesis in transgenic mice over-expressing Artemis

Résumé

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.
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Dates et versions

hal-02881014 , version 1 (25-06-2020)

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P. Rivera-Munoz, V. Abramowski, S. Jacquot, P. Andre, S. Charrier, et al.. Lymphopoiesis in transgenic mice over-expressing Artemis. Gene Ther, 2016, 23 (2), pp.176-86. ⟨10.1038/gt.2015.95⟩. ⟨hal-02881014⟩
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