Histology of dermis and paws of homozygous Lupo mice. (A-B) Hematoxylin and eosin staining of an early stage of dermal inflammation. Inflammatory infiltration is restricted to the connective tissue of the corium and the epithelium (arrowheads, A) and paws (B), showing inflammation starting from the corium (arrow) and spreading to erode the articular cartilage (arrowheads). (C-D) Low-power (C) and high-power (D) images of ears of Lupo (left panels) and WT (right panels) mice, immunostained for the macrophage marker, F4/80+, and counterstained with hematoxylin, showing increased ear thickness, hyperkeratosis, acanthotic epidermis, and increased macrophage infiltration in the external ears of the Lupo mice. (E-F) Low-power (E) and high-power (F) images of paws of Lupo (left panels) and WT (right panels) mice, immunostained for the macrophage marker F4/80+ and counterstained with hematoxylin, showing increased paw thickness, acanthotic epidermis, and increased macrophage infiltration in the footpads of the Lupo mice. Bars, 100 μm.