Figure 9.

A overview chart for mechanism of alleviating mastitis and BMB damage by GED goats with high expression of LYZ. a) According to the regulatory sequence gene editing breeding strategy proposed in this study, GED goats were created by targeted integration of IRS into the LYZ promoter region using the ISDar2‐TnpB system. b) Isolation of GMEC from GED goats for culture and establishment of GMEC organoids. c) E.coli infection of the mammary gland of GED goats increases LYZ expression, which inhibits the activation of PANoptosis, decreases SCC and proinflammatory factor expression in milk, and increases ZO‐1 and occludin expression, thereby alleviating mastitis severity and BMB damage. d) In vitro, a mastitis model was established by treating GMEC with LPS, and the TLR4/MyD88/NF‐κB signaling pathway was activated. e) When the TLR4/MyD88/NF‐κB signaling pathway is activated, a large amount of pro‐inflammatory factors are produced and secreted extracellularly. f) In an in vitro GMEC mastitis model, the PANoptosome can be activated. g) Under inflammatory conditions, IRS upregulates LYZ expression in gene‐edited GMEC. h) In an in vitro GMEC mastitis model, the PANoptosis can be activated. i) Activation of PANoptosis disrupts membrane integrity and permeability. j) Activation of PANoptosis results in the release of a large number of pro‐inflammatory factors. k) In an in vitro GMEC mastitis model, LYZ can exert an anti‐inflammatory role by regulating the expression of HMGB1.