Utilizing nonobese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (ΔHel1), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses.

在K63连接的泛素链的介导下，寡聚的RIG-I或MDA5通过其N端的caspase recruitment domain（CARD）与定位在线粒体膜上的MAVS（也被称为IPS-1、VISA或Cardif）发生相互作用。MAVS能够募集TRAF家族蛋白或IKK完成信号转导，活化IRF3、IRF7或者NF-κB转录因子开启相应基因的转录表达。

MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. [5] MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses.

2015年1月15日 · Here, by reducing MDA5 gene expression we have uncovered a unique IFN-I signature in NOD mice that has led to the expansion of regulatory T cells at the site of autoimmunity and to the protection from T1D, suggesting a new avenue for T1D therapy, in targeting MDA5, that considers both genetic and environmental factors known to alter disease ...

2018年5月1日 · Since T1D is a chronic proinflammatory autoimmune disease involving MDA5, we hypothesized that aberrant MDA5 expression and signaling can contribute to diabetogenic viral-accelerated T1D. NOD mice mutated in Ifih1 that resulted in loss of MDA5 expression (NOD.

2020年6月1日 · By utilizing mice that lack (NOD.Ifih1 KO) or contain a deletion within the helicase 1 domain of MDA5 (NOD.Ifih1 ΔHel1), we can test the hypothesis that reduced MDA5 signaling delays T1D by decreasing IFN-α/β synthesis and debilitating islet-infiltrating macrophage and T cell effector responses.

Utilizing nonobese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (ΔHel1), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses.

We previously demonstrated that CVB3 infection of Non-Obese Diabetic (NOD) mice accelerates T1D, partly due to the activation of melanoma differentiation-associated protein 5 (MDA5)-dependent antiviral responses including IFN-α/β synthesis. Mutations within human IFIH1, the gene encoding MDA5, are correlated with T1D risk.

2022年12月13日 · Utilizing nonobese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (Δ Hel1), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses.

2022年12月13日 · Utilizing non-obese diabetic (NOD) mice lacking Ifih1 expression (KO) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (ΔHel1), we tested the...