Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection.

INTRODUCTION: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. METHOD: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. RESULTS: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. CONCLUSION: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

The study on organ weights, blood physiological and biochemical parameters and immune cells in Rag2 knockout mice / 中国比较医学杂志

Objective To measure the organ weights , blood physiological and biochemical parameters , and immune function of Specific Pathogen Free ( SPF) Rag2 knockout ( KO) mice.Methods Rag2 knockout mice were selected at five and ten weeks , and the organ weights , blood physiological and biochemical parameters were observed .The percentages of CD3+, CD4+, CD8+, CD19+, B220+, NK1.1+, and CD11b+were checked by FCM in Rag2 KO mice at six week of age in terms of its T , B lymphocyte function and NK cell activity .Results Among the same sex group of NOD/SCID mice, the weights of brain, lung, spleen, liver, heart, kidney, and the levels of TBIL, WBC in 10 weeks of age are higher than 5 weeks.At the same age, the weights of heart, kidney, liver, spleen, and the levels of AST, ALP, A/G, GLU, PLT, PCT, WBC, and LYM%in male mice are higher than females.The Rag2 KO mice lacks T cells(0.36 ±0.15)%、CD4+T cells(0.21 ±0.06)%、CD8+T cells(0.23 ±0.07)%、CD19+B cells(0.28 ±0.04)%、B220+B cells(2.03 ±0.42)%).The percentage of NK cells is(24.13 ±3.62)%, and the percentage of granulocytes is (57.20 ±3.85)%.Conclusion The study suggests that the organ weights , blood physiological and biochemical parameters are affected by age and gender in Rag2 KO mice, which main biological characteristics are similar with C 57BL/6J mice.The Rag2 KO mice show the deficiency of T , B cells function .