Table 1.
Axon pathology secondary to mutations in myelin-associated genes and experimental demyelination models
Animal modelAxon phenotypeReferences
Shiverer (Mbp null) Decreased axon caliber/neurofilament phosphorylation, minimal axon degeneration Rosenbluth, 1980; Brady et al., 1999  
Plp1 null Progressive axon loss, axonal spheroids containing multivesicular bodies, disorganized cytoskeletal components, and membranous organelles, impaired axon transport, and microtubule abnormalities Klugmann et al., 1997; Griffiths et al., 1998; Garbern et al., 2002; Edgar et al., 2004; Yin et al., 2016   
Cnp null Mislocalization of voltage-gated sodium channels and Caspr, progressive axon loss, axonal spheroids with accumulations of membranous organelles, impaired axon transport, and impaired formation and maintenance of cytoplasmic channels Lappe-Siefke et al., 2003; Rasband et al., 2005; Snaidero et al., 2017  
Mag null Decreased axon caliber/neurofilament phosphorylation, progressive axon loss, increased susceptibility to EAE/neurotoxic injury, and decreased Cdk5/Erk1/2 kinase activity Fruttiger et al., 1995; Yin et al., 1998; Dashiell et al., 2002; Pan et al., 2005; Nguyen et al., 2009  
EAE Axon loss, irreversible cytoskeletal fragmentation, impaired mitochondrial morphology and trafficking, impaired axon transport, oxidative damage, and increased axoplasmic calcium Siffrin et al., 2010; Nikić et al., 2011; Sorbara et al., 2014; Höflich et al., 2016; Mei et al., 2016  
Lysolecithin Impaired axon transport, increased mitochondrial stationary site size and transport rate, and disrupted nodal architecture Arroyo et al., 2004; Kiryu-Seo et al., 2010; Ohno et al., 2014; Höflich et al., 2016; Schultz et al., 2017  
Cuprizone Axon loss, impaired axon transport, and increased mitochondrial stationary site size Ohno et al., 2014; Sachs et al., 2014; Höflich et al., 2016; Schultz et al., 2017  
DT ablation Axon loss, impaired axon transport, and neurofilament dephosphorylation Traka et al., 2010, 2016; Pohl et al., 2011; Oluich et al., 2012  
Animal modelAxon phenotypeReferences
Shiverer (Mbp null) Decreased axon caliber/neurofilament phosphorylation, minimal axon degeneration Rosenbluth, 1980; Brady et al., 1999  
Plp1 null Progressive axon loss, axonal spheroids containing multivesicular bodies, disorganized cytoskeletal components, and membranous organelles, impaired axon transport, and microtubule abnormalities Klugmann et al., 1997; Griffiths et al., 1998; Garbern et al., 2002; Edgar et al., 2004; Yin et al., 2016   
Cnp null Mislocalization of voltage-gated sodium channels and Caspr, progressive axon loss, axonal spheroids with accumulations of membranous organelles, impaired axon transport, and impaired formation and maintenance of cytoplasmic channels Lappe-Siefke et al., 2003; Rasband et al., 2005; Snaidero et al., 2017  
Mag null Decreased axon caliber/neurofilament phosphorylation, progressive axon loss, increased susceptibility to EAE/neurotoxic injury, and decreased Cdk5/Erk1/2 kinase activity Fruttiger et al., 1995; Yin et al., 1998; Dashiell et al., 2002; Pan et al., 2005; Nguyen et al., 2009  
EAE Axon loss, irreversible cytoskeletal fragmentation, impaired mitochondrial morphology and trafficking, impaired axon transport, oxidative damage, and increased axoplasmic calcium Siffrin et al., 2010; Nikić et al., 2011; Sorbara et al., 2014; Höflich et al., 2016; Mei et al., 2016  
Lysolecithin Impaired axon transport, increased mitochondrial stationary site size and transport rate, and disrupted nodal architecture Arroyo et al., 2004; Kiryu-Seo et al., 2010; Ohno et al., 2014; Höflich et al., 2016; Schultz et al., 2017  
Cuprizone Axon loss, impaired axon transport, and increased mitochondrial stationary site size Ohno et al., 2014; Sachs et al., 2014; Höflich et al., 2016; Schultz et al., 2017  
DT ablation Axon loss, impaired axon transport, and neurofilament dephosphorylation Traka et al., 2010, 2016; Pohl et al., 2011; Oluich et al., 2012  

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