NF1 is a critical regulator of muscle development and metabolism

g.oxfordjournals.org/ D ow nloaded from 2 There is emerging evidence for reduced muscle function in children with Neurofibromatosis type 1 (NF1). We have examined three murine models featuring NF1 deficiency in muscle to study the effect on muscle function as well as any underlying pathophysiology. The Nf1+/- mouse exhibited no differences in overall weight, lean tissue mass, fiber size, muscle weakness as measured by grip strength, or muscle atrophy-recovery with limb disuse, although this model lacks many other characteristic features of the human disease. Next, muscle-specific knockout mice (Nf1muscle-/-) were generated and they exhibited a failure to thrive leading to neonatal lethality. Intramyocellular lipid accumulations were observed by electron microscopy (EM) and Oil Red O staining. More mature muscle specimens lacking Nf1 expression taken from the limb-specific Nf1Prx1-/- conditiona