Collagen-Induced Arthritis Analysis in Rhbdf2 Knockout Mouse

Abstract

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramem-brane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha (TNF-alpha) converting enzyme, which is the molecule responsible for the release of TNF-alpha. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of TNF-alpha release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative TNF-alpha related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to TNF-alpha.