The lymphocyte activation gene-3, LAG3, is a significant regulator of the immune system and recently has been concretely attributed to development in Type 1 Diabetes in diabetes prone mice. Type 1 Diabetes is an autoimmune disease in which cells of the body are mistaken as pathogens and destroyed by the immune system. In Type 1 Diabetes, the cells that are destroyed are the insulin-producing beta cells. This disease is generally characterized by insulitis and beta-cell autoantibodies (Van den Driessche et. al, 2009).
LAG3 may be responsible for the malfunctioning of the immune system and the onset of Type 1 Diabetes. LAG3 plays a large part in regulating T cells, which are critical to fighting infections and diseases. LAG3 both regulates the numbers of T cells in the body and is required for the proper functioning of T cells and Natural Killer cells (Workman et. al, 2009). Moreover, many critical cell types in the immune system express LAG3, including CD4+ and CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells (Workman et. al, 2009). These cells each play important functions in detecting pathogens throughout the body and carrying out the removal of harmful entities.
Lag3 deletion in normal mice has been documented to have minor noticeable changes, with little to no effect on the prevalence of diabetes development (Miyazaki et. al, 1996). However, it has been recently demonstrated that in autoimmune-prone conditions, LAG3 plays a critical role in an early onset of Type 1 Diabetes (Bettini et. al, 2011).
Bettini et. al used non-obese diabetic mice, or NOD mice, to test the control of LAG3 on three important types of cells in the immune system: T cells, natural killer cells and plasmacytoid dendritic cells (2011). NOD mice were the subjects of choice, for they are often used as a mouse model of Type 1 Diabetes (Crawford et al., 2011). Bettini et. al bred NOD mice with a Lag3 mutation, rendering the gene non-functional. The mice were then tested for diabetes onset at various points of development by analysis of urine samples and blood glucose levels.
