Basic Science and Pathogenesis.

Background: Genome-Wide Association Studies (GWAS) identified ApoE4 and Trem2*R47H as two of the strongest genetic risk factors for late-onset Alzheimer's Disease (LOAD). As part of our efforts to develop mouse models that better recapitulate LOAD, at Model Organism Development & Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium at University of California - Irvine, we have created a triple homozygous mouse model that combines our previously developed hAb-KI mice (Jackson Lab #031050), Trem2 (Jackson Lab #034036) and a humanized ApoE4 (Jackson Lab #027894), to evaluate the interactions between aging, hAPOE4, TREM2*R47H, and hAb.

Method: By breeding the hAb-KI, hApoE4 and Trem2, we obtained triple homozygous (HO) mice and we then generated four different groups: WT (C57BL6/J), hAb-KI HO, hAb-KI HO;hApoE4 HO and hAb-KI HO;hApoE4 HO;Trem2 HO.

TDAG8 deficiency reduces satellite glial number and pro-inflammatory macrophage number to relieve rheumatoid arthritis disease severity and chronic pain.

Background: The autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression.