Dr Howlett and colleagues have been interested for many years in the genetics of the autoimmune disease type 1 diabetes. Like other autoimmune diseases, in type 1 diabetes the immune system targets and attempts to destroy particular tissues in the body. Such diseases often affect several individuals in an extended family.
The team has made use of a naturally occurring mouse that spontaneously gets diabetes in a manner very similar to the disease in humans. This has enabled them and others to identify many of the genes that together contribute to the progression of the disease. Most importantly it has transpired that many of the same genes are involved in both mice and humans. Identification of the genes has highlighted important pathways that could be amenable to therapy.
The main benefit from our current research using mice is the discovery of information that can be used to improve the design of human immunotherapy trials for autoimmune diseases, such as type 1 diabetes and multiple sclerosis, both of which are increasing at a rapid rate in industrialised nations. Autoimmune disease involves many interacting cells that have developed and migrated within the autoimmune-prone environment and so the whole body must be analysed to understand the progression of disease over time. Dr Howlett and colleagues make use of a ‘special’ mouse that does not have an immune system of its own but is able to ‘house’ human-derived lymphoid cells that form an effective and functional immune system that is entirely of human origin. This mouse offers the ideal situation in which to test a variety of possible immunotherapies before they go into humans.