The expression of SR calcium transport ATPase and the Na+/Ca2+ exchanger are antithetically regulated during mouse cardiac development and in hypo/hyperthyroidism

The mouse has been used extensively for generating transgenic animal models Lo study cardiovascular disease. Recently, a number of transgenic mouse mo dels have been created to investigate the importance of sarcoplasmic reticu lum (SR) Ca2+ transport proteins in cardiac pathophysiology. However, the e xpression and regulation of cardiac SR Ca2+ ATPase and other Ca2+ transport proteins have not been studied in detail in the mouse. In this study, we u sed multiplex RNase mapping analysis to determine SERCA2, phospholamban (PL B), and Na+/Ca2+ exchanger (NCX-1) gene expression throughout mouse heart d evelopment and in hypo/hyperthyroid animals. Our results demonstrate that t he expression of SERCA2 and PLB mRNA increase eight-fold from fetal to adul t stages, indicating that SR function increases with heart development. In contrast, the expression of the Na+/Ca2+-exchanger gene is two-fold higher in fetal heart compared to adult. Our study also makes the important observ ation that in hypothyroidic hearts the NCX-1 mRNA and protein levels were u pregulated, whereas the SERCA2 mRNA/protein levels were downregulated, In h yperthyroidic hearts, however, an opposite response was identified. These f indings are important and point out that the expression of NCX-1 is regulat ed antithetically to that of SERCA2, during heart development and in respon se to alterations in thyroid hormone levels. (C) 2000 Academic Press.