A general view is that critical genes involved in biological pathways are highly conserved among species. To understand human autoimmune diseases, a great deal of effort has been devoted to the study of murine models that mirror many pathologic properties observed in the human disease. We have found that lymphocytes from humans with different autoimmune disease all carry a common conserved gene expression profile. Therefore, we wanted to determine if lymphocytes from common murine models of autoimmune disease carried a gene expression profile similar to the human profile and if both mouse models carried a shared gene expression profile. We identified numerous differentially expressed genes (DEGs) in the autoimmune strains compared to non-autoimmune strains. However, we found very little overlap in the gene expression profile between human autoimmune disease and murine models of autoimmune disease and between different murine autoimmune models. Our research further confirms that murine models of autoimmunity do not perfectly match human autoimmune diseases.