p66Shc^−/− mice develop lupus-like alopecia. (A) Representative pictures of control (+/+) and p66Shc^−/− (−/−) mice with alopecia. At the bottom, the frequencies of alopecia in the face and scalp or in the back of female (F) and male (M) mice are reported. The incidence of the lesions was not affected by the number of mice per cage. No microorganisms were found by either light or electron microscopy. (B) Histologic analysis of skin sections. H&E stained shows thinning of dermis and reduction in size and number of hair follicles in p66Shc^−/− mice (100×). The inset shows lymphatic infiltration around and within the hair follicles (arrow) (200×) (n ≥ 3). (C) Toluidine blue–stained skin sections display numerous infiltrated mast cells (magenta, M) in p66Shc^−/− mice versus controls (200×). The arrow indicates a degranulating mast cell. The arrowhead shows an infiltrated neutrophil. Loosening of dermal collagen fibers due to edema can be observed. The inset shows an electronic micrograph of an activated mast cell in an alopecic skin section from a p66Shc^−/− mouse, characterized by the presence of abundant large granules throughout the cytoplasm, some of which appear to be releasing their contents to the extracellular space (n ≥ 3). (D) Analysis of Ig deposit by fluorescence staining with FITC-conjugated goat anti–mouse immunoglobulins displays immune complexes deposited in the dermal layer of the skin from p66Shc^−/− mice. Scale bar represents 100 μm (n ≥ 4).