General information

Development

IL15 (Interleukin-15) is a pleiotropic cytokine produced by various activated cells such as mononuclear-macrophages, epidermal cells, and fibroblasts. It exerts biological activities similar to IL2, activating T cells, B cells, and NK cells, and promoting the proliferation and survival of these cells ^[1,2]. We used a transgenic approach in the NPG mouse model to inject the linearized human IL15p-hIL-15 expression sequence into the pronucleus of NPG mice. We selected positive mice with appropriate expression levels from the offspring for breeding.

Phenotype

1. Protein expression analysis

Fig1. Human IL15 expression analysis in heterozygous and homozygous NPG-hIL15 mice by ELISA.

Serum were collected from heterozygous and homozygous NPG-hIL15 mice, and analyzed by ELISA with human IL15 ELISA kit. hIL-15 expression was approximately 50 pg/mL in heterozygous NPG-hIL15, and hIL-15 expression was approximately 98.8 pg/mL in homozygous NPG-hIL15.

2. Levels of immune cell reconstitution after HSC transplantation in hIL15-NPG mice

Fig2. The levels of peripheral blood immune cells after transplantation of CD34+ cell in IL15-NPG mice

Serum were collected from NPG-hIL15 mice with HSC transplantation, compared to HSC-NPG, HSC-hIL15-NPG had a higher hCD56⁺ NK reconstruction level, and a higher subpopulation of differentiated hCD16⁺ NK cells, which remained at a higher level throughout the observed 12 weeks.

NPG-hIL15 Mice Applications

1.Cancer treatment (e.g., lysovirus and Car-T, etc.)

2.Human hematopoietic system and immune system research

3.Regenerative medicine

4.Infectious diseases

5.Human cell and tissue transplantation

6.NK cell development mechanism research

7.Tumor immunotherapy research on NK cells or NK and T cells combined action

8. Antibody-dependent NK cell-mediated toxicity (ADCC) studies

9.CAR-NK efficacy validation

Reference

1. Ali AK, Nandagopal N, Lee SH. IL-15-PI3K-AKT-mTOR: A Critical Pathway in the Life Journey of Natural Killer Cells. Front Immunol. 2015, 6:355.

2. Fehniger TA, Suzuki K, Ponnappan A, et al. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8⁺ T cells. J Exp Med. 2001, 193(2):219-231.