HRC (histidine-rich Ca+ binding protein) was first identified from rabbit, located within the lumen of the sarcoplasmic reticulum (SR) in striated muscle. The SR of striated muscle is an extensive network of membrane tubules and cisternae which stores Ca2+ and releases it rapidly into the cytoplasm upon membrane depolarization. Substantially the mouse homologue of HRC (mHRC) was isolated and characterized. In recent study, HRC binds directly to triadin, which is an integral membrane protein of the SR. Moreover, the interaction of HRC and triadin is Ca2+-sensitive. With many evidences, functional role of HRC in Ca2+ homeostasis in SR has been suggested. In this study, to elucidate the role of mHRC in heart, in vitro adenovirus-mediated transfection was used. As a result, an increased SR Ca2+ storage capacity was observed by adenovirus-mediated transfection in the neonatal rat cardiac myocytes culture system. Secondly, in vivo transgenic mouse overexpressing mHRC under the control of mouse 慣-myosin heavy chain (慣-MHC) and human growth hormone (HGH) promoter were generated. Three lines (64, 66, and 78 line) were obtained and studied. Each line appears to have a different mHRC protein overexpression level. TG mouse and negative littermate were discriminated by Polymerase Chain Reaction (PCR) and southern blotting. By northern blotting, atrial natriuretic factor (ANF), which is a cardiac hypertrophy marker gene, was increased in transcriptional level in left ventricle of TG mouse. According to echocardiography, interventricular septal thickness was increased about 2-folds in TG mouse heart compared to wild type mouse heart, but the difference of fractional shortening or ejection function was not observed. As a result, overexpressing mHRC in mouse heart led to non-pathological hypertrophy in TG heart. This study suggests mHRC play a role in Ca2+ homeostasis in SR of mouse heart and might be an important factor of cardiac hypertrophy.