Abstract
In 2009–2010, an unusual lymphoproliferative disease was identified in multiple siblings from successive litters of Manx cats, suggesting a genetic predisposition to development of this disease. Presentation of disease in the cats had multiple similarities with the human disease ALPS, a rare inherited disorder that causes persistent lymphoproliferation, together with variable manifestations of autoimmunity and increased susceptibility to neoplasia. The majority of human ALPS patients have inherited Fas gene mutations, causing defective apoptosis of lymphocytes, although for a proportion of ALPS patients the underlying genetic mutations remain unknown. In order to identify the likely mode of inheritance of the disease, further matings of potential carrier cats are in progress. Studies to investigate the potential role of abnormalities in the Fas gene in the development of the disease in cats are also proposed. Identifying and further characterising the nature and mechanism of the disease in cats may allow better understanding of the development, progression, and treatment of ALPS in humans.