Activated KRAS Alters Epidermal Homeostasis of Mouse Skin, Resulting in Redundant Skin and Defective Hair Cycling

The study examined the effects of activating the KrasG12D allele in mouse skin, which resulted in redundant skin, papillomas, shortened nails, and hair loss due to disrupted epidermal homeostasis and defective hair cycling. KrasG12D activation led to hyperproliferation of basal keratinocytes without affecting their differentiation, causing overgrowth of follicular epithelium and resistance to apoptosis in outer root sheath cells. Despite the presence of bulge cells, hair cycling was impaired, leading to progressive hair loss. These findings highlighted the role of RAS signaling in skin and hair morphogenesis and provided insights into similar human RAS/MAPK syndromes.