Myostatin is a negative regulator of muscle growth. Loss of myostatin has been shown to cause increase in skeletal muscle size and improve skeletal muscle function and fibrosis in the dystrophindeficient mdx mouse, an animal model for Duchenne muscular dystrophy. We evaluated whether lack of myostatin has an impact on cardiac muscle growth and fibrosis in vivo. Using genetically modified mice we assessed whether myostatin absence induces similar beneficial effects on cardiac function and fibrosis. Cardiac mass and ejection fraction were measured in wild type, myostatin-null, mdx and double mutant mdx/myostatinnull mice by high resolution echocardiography. Heart mass, myocyte area and extent of cardiac fibrosis were determined post mortem. Myostatin-null mice do not demonstrate ventricular hypertrophy when compared to wild type mice as shown by echocardiography (ventricular mass 0.69± 0.01 g vs.0.69±0.018 g, P = 0.75, respectively) and morphometric analyses including heart/body weight ratio (5.39±0.45mg/g vs. 5.62±0.58mg/g, P = 0.59 respectively) and cardiomyocyte area 113.67±1.5μm 2 , 116.85±1.9μm 2 ; P = 0.2). Moreover, absence of myostatin does not attenuate cardiac fibrosis in the dystrophin deficient mdx mouse model for DMD (12.2% vs. 12% respectively, P = 0.88). The physiological role of myostatin in cardiac muscle appears significantly different than that in skeletal muscle as it does not induce cardiac hypertrophy and does not modulate cardiac fibrosis in mdx mice.

The genetic basis of oculopharyngeal muscular dystrophy (OPMD) is a short expansion of a polyalanine tract (normal allele: 10 alanines, mutant allele: 11–17 alanines) in the nuclear polyadenylate binding protein PABPN1 which is essential for controlling poly(A) tail length in messenger RNA. Mutant PABPN1 forms nuclear inclusions in OPMD muscle. To investigate the pathogenic role of mutant PABPN1 in vivo, we generated a ligand-inducible transgenic mouse model by using the mifepristone-inducible gene expression system. Induction of ubiquitous expression of mutant PABPN1 resulted in skeletal and cardiac myopathy. Histological changes of degenerative myopathy were preceded by nuclear inclusions of insoluble PABPN1. Downregulation of mutant PABPN1 expression attenuated the myopathy and reduced the nuclear burden of insoluble PABPN1. These results support association between mutant PABPN1 accumulation and degenerative myopathy in mice. Resolution of myopathy in mice suggests that the disease process in OPMD patients may be treatable.

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The proposition Extended Semantic Network is an innovative fool for Knowledge Representation and Ontology conslruetion. which not only infers meanings but looks for sets of associations between nodes as opposed to the present method of keyword association, I'iie objective here is to achieve semi-stipervised knowledge represenration technique with good accuracy and mininuini human intervention-This is realized by <>blaifiing a technical cooperation between mathematical and mind models to harvest their collective intelligence.