Late-onset megaconial myopathy in mice lacking group I Paks

Skeletal Muscle
Giselle A JosephRobert S Krauss

Abstract

Group I Paks are serine/threonine kinases that function as major effectors of the small GTPases Rac1 and Cdc42, and they regulate cytoskeletal dynamics, cell polarity, and transcription. We previously demonstrated that Pak1 and Pak2 function redundantly to promote skeletal myoblast differentiation during postnatal development and regeneration in mice. However, the roles of Pak1 and Pak2 in adult muscle homeostasis are unknown. Choline kinase β (Chk β) is important for adult muscle homeostasis, as autosomal recessive mutations in CHKβ are associated with two human muscle diseases, megaconial congenital muscular dystrophy and proximal myopathy with focal depletion of mitochondria. We analyzed mice conditionally lacking Pak1 and Pak2 in the skeletal muscle lineage (double knockout (dKO) mice) over 1 year of age. Muscle integrity in dKO mice was assessed with histological stains, immunofluorescence, electron microscopy, and western blotting. Assays for mitochondrial respiratory complex function were performed, as was mass spectrometric quantification of products of choline kinase. Mice and cultured myoblasts deficient for choline kinase β (Chk β) were analyzed for Pak1/2 phosphorylation. dKO mice developed an age-related myopathy. ...Continue Reading

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Citations

May 12, 2019·Cells·Lisbeth Liliendal Valbjørn MøllerLykke Sylow

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Methods Mentioned

BETA
scraping
electrophoresis
Assay
X-ray
electron microscopy

Software Mentioned

GTEx
ggplot2
GraphPad Prism
Image J
R
ProgRes Mac CapturePro

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