used SAMP1/YitFc mice that spontaneously develop CD-like symptoms and found that exogenous E2 administration suppressed intestinal inflammation in male mice but not in female mice, which may be because the immunoprotective effects mediated by distinct ER isoforms were impaired in T cells from SAMP-Female mice (45). The gene discussed is XPNPEP1; the disease is Cowden disease.