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, 59 (4), 553-60

Muscular Dystrophy in Adult and Aged anti-NGF Transgenic Mice Resembles an Inclusion Body Myopathy

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Muscular Dystrophy in Adult and Aged anti-NGF Transgenic Mice Resembles an Inclusion Body Myopathy

S Capsoni et al. J Neurosci Res.

Abstract

The role of nerve growth factor (NGF) and its receptors in the physiology of skeletal muscles has not been extensively studied in animal models. We describe the production of transgenic lines of mice expressing a neutralizing antibody against NGF (alphaD11) and the morphological and histochemical analysis of skeletal muscles from adult and aged anti-NGF mice. This study reveals that the chronic deprivation of NGF results in a decreased size of myofibers of dorsal and hindlimb muscles in adult but not in postnatal day (P)2 mice. In myofibers from adult anti-NGF mice, the presence of central nuclei, vacuolization of the cytoplasm, and inflammatory cell infiltration was observed. The immunohistochemical analysis of these muscular fibers revealed an upregulation of p75 expression, a decrease in adenosine triphosphatase (ATP)ase activity, and a subsarcolemmal Congo Red-positive staining. Immunostaining with an antibody against amyloid precursor protein showed an increased labeling of the cytoplasm of myofibers from adult and aged anti-NGF mice. These features are reminiscent of human myopathies, such as inclusion body myositis. We conclude that NGF deficits might be relevant for a class of human myopathies.

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