Biomol Ther  
Collagen-Induced Arthritis Analysis in Rhbdf2 Knockout Mouse
Min-Young Lee1,2, Ju-Seong Kang1, Ryeo-Eun Go2, Yong-Sub Byun1, Young Jin Wi3, Kyung-A Hwang2, Jae-Hoon Choi3, Hyoung-Chin Kim1, Kyung-Chul Choi2,* and Ki-Hoan Nam1,*
1Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon 28116,
2Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644,
3Department of Life Science, College of Natureal Sciences, Research Institute of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea
E-mail: kchoi@cbu.ac.kr (Choi KC), namk@kribb.re.kr (Nam KH)
Tel: +82-43-261-3664 (Choi KC), +82-43-240-6561 (Nam KH)
Fax: +82-43-267-3150 (Choi KC), +82-43-240-6569 (Nam KH)
Received: May 7, 2017; Revised: July 21, 2017; Accepted: July 24, 2017; Published online: December 8, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha (TNF-α) converting enzyme, which is the molecule responsible for the release of TNF-α. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of TNF-α release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative TNF-α 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-α.
Keywords: Rhbdf2 knockout mouse, Collagen-induced arthritis, TNF-α


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