In contrast, a squamous epithelium-specific Nrf2 deficiency in the context of systemic Keap1-deficient mice (Keap1−/−::Nrf2Flox/Flox::K5-Cre, referred to as Nrf2-deficient in oesophagus and Keap1-null mice, NEKO) corrects the hyperkeratosis of the oesophagus and subsequent lethality, while full activation of Nrf2 is observed in most tissues, with the exception of the oesophagus and skin. This evidence concerns the gene KEAP1 and Hyperkeratosis.