Development of a sodium/iodide symporter (NIS)-transgenic mouse for imaging of cardiomyocyte-specific reporter gene expression

Abstract

Development of a small animal imaging system for differentiated cell-specific reporter gene expression will enable us to image cellular differentiation in vivo. In this study, we developed a sodium/iodide symporter (NIS)-transgenic mouse in which NIS is constitutively expressed as an imaging reporter gene only in cardiomyocytes. METHODS: To express NIS gene in cardiomyocytes, alpha-myosin heavy chain (alpha-MHC)-NIS was constructed and used for the production of NIS-transgenic mice. Twelve lines of positive founder were obtained. The adequacy of the transgenic mouse model was tested by in vivo scintigraphy, microPET, and a biodistribution study. RESULTS: The myocardium of transgenic mice showed rapid and intense uptake of 131I, which was much higher than that of the thyroid, and also showed long retention by gamma-camera pinhole imaging. The relative uptake ratio of the heart of transgenic mice was 4.6 +/- 1.5, which was 3.8 +/- 1.2 times higher than that of control wild-type mice. The uptake of the heart was completely blocked by oral administration of KClO4, an NIS inhibitor. The heart of transgenic mouse was also clearly and intensely visualized on microPET using 124I. Biodistribution data of these mice showed the uptake of 40-160 %ID/g (percentage injected dose per gram of tissue) of (99m)Tc-pertechnetate in the heart compared with 40-60 %ID/g in the stomach, respectively. NIS expression in the myocardium was confirmed by immunohistochemistry using a NIS-specific antibody. CONCLUSION: We developed a transgenic mouse model to image cardiomyocytes with a gamma-camera and microPET using an alpha-MHC promoter and NIS. The transgenic mouse can be used as an imaging model for cardiomyocyte-specific reporter gene expression and cellular differentiation into cardiomyocytes after cardiac stem or progenitor cell transplantation.