173 A Model to Unravel Pathways Underpinning Palmoplantar Homeostasis and Disease

Abstract

Tylosis with oesophageal cancer (TOC) is a rare syndrome associated with focal non-epidermolytic palmoplantar keratoderma (NEPPK), a high, lifetime risk of developing oesophageal squamous cell carcinoma (OSCC), and gain-of-function mutations in RHBDF2 (encoding iRhom2). To date, there is a lack of a useful and representative model to study the development of NEPPK and OSCC in vivo, which might aid our understanding of hyperproliferative skin disease and cancer predisposition. CRISPR-Cas9 was used to generate a novel mouse model of TOC that contains a heterozygous Rhbdf2I156T/+ mutation which mirrors the UK TOC family mutation, RHBDF2I186T/+.