The epidermis of S100a4 Sharpin-/- mice contained apoptotic keratinocytes and had various degrees of acanthosis and orthokeratotic hyperkeratosis resulting in mild to moderate increase of epidermal thickness (Figs 3 and 4F) which were less severe than seen in the ubiquitously deleted Sharpin or Krt14 Sharpin-/- mice. This evidence concerns the gene S100A4 and Hyperkeratosis.