Lan Weiss, Kwang-Mook Jung, Angele Nalbandian, Katrina Llewellyn, Howard Yu, Lac Ta, Isabela Chang, Marco Migliore, Erica Squire, Faizy Ahmed, Daniele Piomelli, Virginia Kimonis
Knock-in homozygote VCPR155H/R155H mutant mice are a lethal model of valosin-containing protein (VCP)-associated inclusion body myopathy associated with Paget disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Ceramide (d18:1/16:0) levels are elevated in skeletal muscle of the mutant mice, compared to wild-type controls. Moreover, exposure to a lipid-enriched diet reverses lethality, improves myopathy and normalizes ceramide levels in these mutant mice, suggesting that dysfunctions in lipid-derived signaling are critical to disease pathogenesis...
February 25, 2021: Human Molecular Genetics