Forsøksdyr: Breeding of NSGS mice

Godkjenningsdato 23.05.2018

Godkjenningsperiode 02.07.2018-02.07.2022

These mice, which are immunodeficient, permit the engraftment of human cell lines and primary human samples. As such they are critical to the development of disease models, which accurately predict the human disease in a mouse model.

The expected harm/severity for the animals will be low.

The Il2rg-/-specific NOD.SCID background supports human and murine hematopoietic cell engraftment, and suppresses human erythropoiesis, enhances human myelopoiesis, and reduces human B-lymphopoiesis in mice after transplant of human bone marrow or fetal liver cells. It is our desire to breed this strain for the development of relevant primary preclinical xenografts of hematological malignancies.
We expect to use 1500 NSGS mice. They contain three transgenes, human interleukin-3 (IL-3), human granulocyte/macrophage-stimulating factor (GM-CSF), and human Steel factor (SF) gene, each driven by a human cytomegalovirus promoter/enhancer sequence. These mice are maintained on the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice (Stock No. 005557) background. These mice constitutively produce 2-4 ng/ml serum levels of human IL-3, GMCSF and SF.
The only in vitro alternative is the use of cell lines and primary patient material in culture. However, these results do not always translate into efficacy in intact biological entities .In addition, we can not using cell culture studies evaluate systemic toxic or efficacy effects, thus the use of animal models is unavoidable. We'll try to reduce the number of animals and avoid having a surplus, using an optimum number of breeding pairs. Experienced technicians will closely monitor animals and they can very early discover any sign of illness and take the decision of euthanasia, if necessary. All cages will have environmental enrichment available at Vivarium.