Muscular dystrophy in adult and aged anti-NGF transgenic mice resembles aninclusion body myopathy

The role of nerve growth factor (NGF) and its receptors in the physiology o f skeletal muscles has not been extensively studied in animal models, We de scribe the production of transgenic lines of mice expressing a neutralizing antibody against NGF (alpha D11) and the morphological and histochemical a nalysis of skeletal muscles from adult and aged anti-NGF mice. This study r eveals that the chronic deprivation of NGF results in a decreased size of m yofibers 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 nu clei, vacuolization of the cytoplasm, and inflammatory cell infiltration wa s observed. The immunohistochemical analysis of these muscular fibers revea led an upregulation of p75 expression, a decrease in adenosine triphosphata se (ATP)ase activity, and a subsarcolemmal Congo Red-positive staining. Imm unostaining with an antibody against amyloid precursor protein showed an in creased labeling of the cytoplasm of myofibers from adult and aged anti-NGF mice. These features are reminiscent of human myopathies, such as inclusio n body myositis, We conclude that NGF deficits might be relevant for a clas s of human myopathies, (C) 2000 Wiley-Liss, Inc.