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Merck

NF1 is a critical regulator of muscle development and metabolism.

Human molecular genetics (2013-10-29)
Kate Sullivan, Jad El-Hoss, Kate G R Quinlan, Nikita Deo, Fleur Garton, Jane T C Seto, Marie Gdalevitch, Nigel Turner, Gregory J Cooney, Mateusz Kolanczyk, Kathryn N North, David G Little, Aaron Schindeler
摘要

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 and Oil Red O staining. More mature muscle specimens lacking Nf1 expression taken from the limb-specific Nf1Prx1(-/-) conditional knockout line showed a 10-fold increase in muscle triglyceride content. Enzyme assays revealed a significant increase in the activities of oxidative metabolism enzymes in the Nf1Prx1(-/-) mice. Western analyses showed increases in the expression of fatty acid synthase and the hormone leptin, as well as decreased expression of a number of fatty acid transporters in this mouse line. These data support the hypothesis that NF1 is essential for normal muscle function and survival and are the first to suggest a direct link between NF1 and mitochondrial fatty acid metabolism.

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Sigma-Aldrich
Anti-GAPDH,克隆6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
抗-瘦素 兔抗, affinity isolated antibody, buffered aqueous solution