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Calreticulin mutant mice

Heart is a vital organ that pumps blood to all body parts of an organism through synchronous contraction and relaxation movements of the cardiac muscle. Homeostasis of cardiac muscle is thus necessary for normal heart functioning. Fine tuning of the cardiac muscle is maintained by numerous signal transduction pathways which are not only responsible for physiological functions, but pathological lesions as well. Many intrinsic or extrinsic stimuli like physical stress, pressure overload, hypertension, etc. disturbs cardiac homeostasis and affects signal transduction pathways causing disease phenotype such as hypertrophy, cardiomyopathy, and consequent heart failure. The most unique characteristic of cardiomyocytes is that they are terminally differentiated and do not grow in number postnatally, they only grow in size by lateral/longitudinal hypertrophy. Hypertrophy is also induced in cardiomyocytes to overcome acute wall tension caused by various biochemical stresses. At molecular level, several signalling pathways and interacting networks have been implicated with the heart’s molecular response to physiological and/or pathological biomechanical stress, reviewed in detail elsewhere [1‐4]. Calcineurin, a Ca2+‐calmodulin activation dependent serine‐threonine phosphatase is one of the key signaling molecules strongly linked to cardiac hypertrophy [5‐8]. Its prohypertrophic effects are well established through series of in vitro and in vivo studies and is highly correlated with human patients of cardiac hypertrophy and cardiomyopathy [6,9]. Moreover, Calcineurin signaling is found to be interconnected with many other important hypertrophic pathways, such as those controlled by glycogen synthase kinase (GSK) 3β and mitogenactivated protein (MAP) kinase signaling [3,10]. Interestingly, Rho family of small GTPase proteins, consisting of Rho, Rac, and Cdc42 subfamilies regulate the sarcomere organization in cardiomyocytes, one of the hallmarks of hypertrophy [11]. These GTPase effectors are also upstream of a very important cardiac signaling molecule, serum response factor (SRF)