Cachexia and Graft-Versus-Host Disease-Type Skin Changes in Keratin Promoter-Driven TNF Alpha Transgenic Mice

The study investigated the effects of TNF alpha expression in keratinocytes using transgenic mice with a keratin-14 promoter driving human TNF alpha expression. The mice exhibited halted weight gain, retarded hair growth, inhibited adipose production, and signs of fibrosis and immune infiltration in the skin. Over time, the epidermis showed increased stratum corneum and necrosis, leading to cachexia and necrosis within 3-5 weeks. The findings suggested that TNF alpha expression by keratinocytes contributed to inflammatory and graft-versus-host-disease-like responses in the skin and other tissues, as TNF alpha entered the bloodstream from stratified squamous epithelia. This study provided insights into the effects of TNF alpha in transgenic animals.