In this study, male TX mice with an ATP7B gene defect background were used as WD model mice (18, 19), and it was found that the content of copper in hypothalamus and pituitary tissues, abnormal tissue morphology and organelle ultrastructure, increased apoptosis rate, decreased serum GnRH, LH, FSH, T, and fertility decreased significantly, and the phosphorylation level of ERK1/2 was significantly downregulated in TX mice with WD. This evidence concerns the gene MAPK3 and Wilson disease.