The signal and all of the immunoglobulin (Ig)-V-like exon of the CD274 antigen (Cd274) gene were replaced with a neomycin resistance cassette, abolishing PD-L1 gene expression. PD-L1 is one of two ligands for PD-1 and is upregulated on antigen presenting cells (APCs), activated T cells, myeloid cells, dendritic cells (DCs). It is also expressed on hematopoietic and parenchymal cells. PD-1 is an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity by negative regulation of T cell responses. These mice are more susceptible to T cell-mediated tissue damage from autoimmune diabetes. They get accelerated diabetes after 2 generations of NOD backcrossing. All mice display accelerated diabetes between 4-7 weeks of age. When treated with anti-CD3 these mice develop a wasting disease between 12 and 20 weeks of age characterized by sudden deterioration, weight loss, and inflammation in the heart and skeletal muscles. This wasting disease leads to death within 3-5 days of development of illness. As homozygotes develop diabetes early, this line should be maintained as heterozygotes, although they also develop diabetes. The Jackson Laboratory 2024, used with permission.