Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates active iodide uptake in thyroid follicular epithelial cells. NIS is also expressed in non-thyroid tissues, such as salivary gland, stomach and lactating mammary gland. NIS-mediated iodide uptake is the basis for targeted radionuclide imaging and ablation of tumors expressing NIS. Thus, it is of clinical significance to selectively increase NIS expression in thyroid or breast tissue to facilitate NIS-mediated radionuclide imaging and therapy in patients with thyroid cancer or breast cancer. In addition, it is also desired to selectively decrease NIS expression in non-targeted tissues to eliminate unwanted side effects of NIS-mediated radionuclide therapy. To examine NIS transcriptional regulation in vivo, we engineered a NISlucYFP/wt knock-in mouse, in which expression of the reporter gene, luciferase-YFP fusion gene, is driven by endogenous NIS promoter. Dual reporter gene, the firefly luciferase gene fused with YFP gene, was inserted into NIS locus at the upstream of NIS start codon by homologous recombination. Targeted ES cells were screened by Southern blot assay, and NISLucYFP/wt knock-in heterozygous mice were screened by PCR. IVIS imaging of the NISlucYFP/wt knock-in mouse showed that luciferase is expressed in thyroid, salivary gland, as well as mammary gland, indicating that NIS expression in these tissues are mainly controlled at transcriptional level. We also found that luciferase expression is further increased in thyroid tissues of animals supplemented with low-iodine diet and in lactating mammary gland. Taken together, IVIS imaging of cells derived from NISLucYFP/wt knock-in mouse will greatly facilitate high throughput screening for factor(s) selectively increase/decrease NIS expression in tissues of interest.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA