In this strain, a neo cassette replaces replace 1.9 kb, including exon 2, of the solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 (Slc7a2) gene, abolishing membrane bound CAT2 activity. Mice homozygous for this Cat2-/- allele are viable and fertile. CAT2 is a membrane associated protein involved in the cellular uptake of cationic amino acids such as arginine, lysine and ornithine. CAT2 plays a regulatory role in the activation of macrophages. Arginine is a substrate for nitric oxide synthase (NOS) during the production of nitric oxide (NO). The release of NO by inflammatory cells contributes to the progression of diseases such as cancer, arthritis, inflammatory bowel disease, Crohn's disease, and atherosclerosis. CAT2 plays a role in controlling inflammation and IL-17 activation in an injury model of colitis. These Cat2-/- mice exhibit a reduction in NO biosynthesis in macrophages. They have increased numbers of memory T cells and activated dendritic cells in their lungs. When infected with Helicobacter pylori these mice display suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor. They exhibit altered cytokine expression.
