Collagen-Induced Arthritis Analysis in Rhbdf2 Knockout Mouse

Area of Science:

• Immunology
• Genetics
• Biochemistry

Background:

• Rhomboid family member 2 (Rhbdf2) is an inactive serine protease homolog.
• Rhbdf2 is crucial for the maturation of TNF-α converting enzyme, regulating TNF-α release.
• Tumor necrosis factor-alpha (TNF-α) plays a key role in inflammatory diseases like arthritis.

Purpose of the Study:

• To investigate the role of Rhbdf2 in collagen-induced arthritis (CIA) by generating Rhbdf2 knockout (KO) mice.
• To assess the impact of impaired TNF-α release on CIA development and severity.
• To evaluate physical function loss in CIA using grip strength and rota-rod tests.

Main Methods:

• CRISPR/Cas9 technology was used to generate Rhbdf2 KO mice.
• Collagen-induced arthritis (CIA) was induced in Rhbdf2 mutant mice using chicken collagen type II.
• Disease severity was assessed via clinical scores, histopathological analysis, rota-rod, and grip strength tests.

Main Results:

• Rhbdf2 KO mice exhibited significantly reduced clinical severity of CIA.
• Histopathological analysis confirmed the alleviation of arthritis in Rhbdf2 mutant mice.
• Grip strength testing proved effective in evaluating CIA-induced physical functional deficits.

Conclusions:

• The Rhbdf2 gene significantly influences the induction and severity of collagen-induced arthritis.
• Targeting Rhbdf2 may offer a therapeutic strategy for TNF-α related inflammatory diseases.
• Impaired TNF-α release due to Rhbdf2 deficiency ameliorates CIA pathogenesis.