Mouse model with physiological expression of humanized MHCII and auxiliary molecules for preclinical studies
We introduce a groundbreaking mouse model with physiological expression of MHCII and auxiliary molecules, including chimeric human-mouse HLA-DRA, HLA-DRB1, CD74, CD4, and LAG3. This innovative approach ensures optimized expression on both thymus cells and antigen-presenting cells, closely resembling human RA. These mice exhibit human-like allelic susceptibility, robust T cell response, and unique activation of B cells producing anti-citrullinated protein antibodies (ACPAs). This model is ideal for preclinical testing of candidate drugs such as anti-inflammatory drugs, biologicals, tolerogenic vaccines, and disease-modifying anti-rheumatic drugs.
Three HLA-DRB1 variants available
The most important genetic locus contributing to development of rheumatoid arthritis (RA) is the MHCII region, accounting for 30-50% of the total genetic risk of RA. Disease-associated loci include several variants; the DRB1*04:01 is the predominant allele in the Caucasian population whereas the DRB1*04:05 is the predominant allele in the East Asian population. In contrast, DRB1*04:02 is an allele with only weak or no association with RA and may even be associated with protection from RA.
Our genetically modified mice:
Primus with HLA-DRB1*04:01
Secundus with HLA-DRB1*04:02
Quintus with HLA-DRB1*04:05
Challenges the model addresses
Rheumatoid arthritis (RA) is a complex autoimmune disease with a significant genetic component. The most crucial genetic locus contributing to RA development is the MHCII region, accounting for 30-50% of the total genetic risk. Current experimental animal models, such as transgenic and minimally humanized mice, have limitations in mimicking human-like physiological MHCII expression, leading to sub-optimal results in drug testing and understanding disease mechanisms. Our unique mouse model addresses these challenges by offering a more accurate representation of RA, including physiological expression of MHCII and associated molecules, leading to better preclinical testing and understanding of RA.
Benefits
We believe the model revolutionizes preclinical testing and drug development for RA and other immune mediated diseases.
The benefits include:
- Improved understanding of RA mechanisms and genetic determinants
- Enhanced preclinical testing of candidate drugs, leading to more effective therapies
- Identification of novel therapeutic targets and strategies
- Reduction in the time, cost and risks of drug development
Our unique models contribute to better prediction, prevention, diagnosis, and treatment of RA and other autoimmune diseases.
For more information and inquiries for licensing, contact us at: info@vacara.se
References
Romero-Castillo L, Li T, Do NN, Sareila O, Xu B, Hennings V, Xu Z, Svensson C, Oliveira-Coelho A, Sener Z, Urbonaviciute V, Ekwall O, Burkhardt H, Holmdahl R. Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association. Adv Sci (Weinh). 2024 Jun;11(23):e2401513. doi: 10.1002/advs.202401513.