Related Experiment Video
Updated: Oct 10, 2025
The CYP2D6 Animal Model: How to Induce Autoimmune Hepatitis in Mice
Published on: February 3, 2012
C6orf120 gene knockout in rats mitigates concanavalin A‑induced autoimmune hepatitis via regulating NKT cells
Yuan-Ni Wu1, Rui Zhang2, Xin-Cheng Song1
1Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing 100015, China.
Objective:
To elucidate the role of the functional unknown gene C6orf120 in the pathogenesis of AIH and its mechanism of action, using C6orf120 knockout rats.
Methods:
An autoimmune hepatitis model was established with 35 mg/kg intravenous injection of concanavalin A (Con A) in C6orf120-knockout (C6orf120-/-) and wild-type (WT) rats. Rats were sacrificed after administering Con A for 0, 12, and 24 h. The peripheral blood, liver, spleen, and mesenteric lymph nodes were collected for follow-up studies.
Results:
C6orf120 knockout significantly decreased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and improved the histological damage in Con A-induced autoimmune liver injury.Loss of C6orf120 function significantly increased the frequency of CD3+ CD161+ NKT cells in the peripheral blood, liver, and spleen; downregulated the expression of CD314 (NKG2D) in the liver, spleen, and mesenteric lymph nodes; reduced the expression of inflammatory cytokines and chemokines; and suppressed the mRNA and protein expression of Fas and FasL in the liver. Additionally, C6orf120 knockout significantly downregulated the expression of p-JAK1, p-JAK2, p-STAT1, and p-STAT3 in liver tissue.
Conclusion:
The protective effect of C6orf120 knockout against Con A-induced hepatitis may be due to the inhibition of NKT cell activation, restriction of cytokine and chemokine activities, inhibition of JAK-STAT and Fas/FasL signaling pathway activation, and reduction in liver inflammation and hepatocyte apoptosis.
Insights
Gene C6orf120 knockout protects against autoimmune hepatitis by inhibiting NKT cell activation and inflammatory pathways. This study reveals C6orf120
Area of Science:
- Immunology
- Hepatology
- Genetics
Background:
- Autoimmune hepatitis (AIH) is a severe liver disease with complex pathogenesis.
- The role of the C6orf120 gene in AIH remains largely unknown.
Purpose of the Study:
- To investigate the function of C6orf120 in autoimmune hepatitis.
- To elucidate the underlying mechanisms of C6orf120's involvement in AIH pathogenesis.
Main Methods:
- Established a concanavalin A (Con A)-induced autoimmune hepatitis model in C6orf120-knockout and wild-type rats.
- Analyzed liver, blood, spleen, and lymph node tissues for immunological and molecular changes.
Main Results:
- C6orf120 knockout significantly reduced liver injury markers (ALT, AST) and histological damage.
- Knockout mice showed altered NKT cell frequency, downregulated NKG2D, inflammatory cytokines, Fas/FasL, and JAK-STAT signaling.
- C6orf120 deficiency suppressed inflammatory responses and hepatocyte apoptosis.
Conclusions:
- C6orf120 knockout confers protection against Con A-induced hepatitis.
- The protective effect is mediated by inhibiting NKT cell activation, inflammatory signaling pathways (JAK-STAT, Fas/FasL), and reducing liver inflammation.
