Grant: Project Grant

We have discovered a family of proteins that are found to be highly expressed in heart cells which we named SLMAPs. We found that these proteins are derived from a single gene in humans by cut and paste mechanisms to generate many different variants or isoforms. Studies have linked mutations in the SLMAP gene with dilated cardiomyopathy leading to debilitation and death of Brugada patients as well as diabetic retinopathy . With funding from CIHR we have generated mouse models to interrogate the function of SLMAPs specifically in the heart. Using gene targeting approaches we have created mice with specific expression of the different SLMAP products in the heart with a view to study their functions. We have also created mice with specific deletion of some of the products in the myocardium to see any impact in the developing embryo versus after birth to discover the functions of SLMAPs at various stages of early heart development and during cardiac aging. Our data from the in vivo manipulation of SLMAPs indicates that these proteins are critically important for developing the normal myocardium in the embryo. Further, we have found that manipulation of SLMAP isoforms in the heart after birth also leads to a role of these proteins as protectors of the myocardium. The generation of mouse models with cardiac specific manipulation of the various SLMAP proteins at various stages of heart development and aging has been expensive and time consuming. We are now poised to define the precise roles of these proteins in the heart and our mouse models will to be valuable sources of discovery and drug/therapeutic development in both congenital heart disease as well as chronic forms of the disorder