Background/Purpose: The differences between human and mouse immune systems make it challenging to accurately reflect the immunopathogenesis of autoimmune diseases in patients. Therefore, translational research needs to shift focus from mouse immunology to human immunology. In addressing these challenges, the HSC-NCG-M mice have emerged as a valuable model. Gempharmatech developed the HSC-NCG-M mouse model to support the development of human T, B, NK, and myeloid cells more effectively. The HSC-NCG-M mouse model is genetically engineered on the severe immunodeficient NCG strain and produces human granulocyte/macrophage colony-stimulating factor 2 (GM-CSF, also known as CSF2), interleukin-3 (IL-3), and stem cell factor (SCF, also known as KITLG).

Methods: This study describes the construction process of the RA model in HSC-NCG-M mice. Female NCG-M mice (4-6 weeks old) were engrafted with CD34⁺ HSC after irradiation. The RA model was induced by injecting Complete Freund’s Adjuvant (CFA) into the foot pads of the hind limbs. The body weight, graft-versus-host disease (GvHD) score and the development of arthritis in the hind limbs of the mice were monitored three times a week. The arthritis score for each mouse was obtained by summing the scores for both hind limbs. The volume of the left and right hind limbs, including the joint of the paw and ankle, was measured three times a week using a claw measuring instrument until the end of the experiment.

Results: In the CFA-induced RA model based on HSC-NCG-M mice, there was an increasing number of human CD4+ T lymphocytes, Th17, Treg, and monocytes in peripheral blood, along with elevated IL-6 levels, which closely resembled clinical phenotypes of RA patients. Compared to the control group, HSC-NCG-M mice injected with CFA in the foot pads showed increased arthritis scores and swelling thickness in the hind limbs.

Conclusion: This model develop a fully functional human immune system capable of innate and adaptive immune responses. The CFA-induced RA model primarily involves the human immune system and closely resembles human RA patients. Therefore, the HSC-NCG-M mouse model is an appropriate model for studying RA, as it involves the engagement of the human immune system.

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunopathogenesis-and-preclinical-trials-in-a-humanized-mouse-model-of-rheumatoid-arthritisra/