CMT 1A: Nerve-dependent changes in skeletal muscle myosin heavy chain after expe

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Muscle Nerve. 2008 Nov 18;38(6):1572-1584.

Nerve-dependent changes in skeletal muscle myosin heavy chain after

experimental denervation and cross-reinnervation and in a

demyelinating mouse model of Charcot-Marie-Tooth disease type 1A.

Maggs AM, Huxley C, SM.

Randall Division for Cell Biophysics, King's College London, UK.

Innervation regulates the contractile properties of vertebrate muscle

fibers, in part through the effect of electrical activity on

expression of distinct myosins. Herein we analyze the role of

innervation in regulating the accumulation of the general,

maturational, and adult forms of rodent slow myosin heavy chain

(MyHC) that are defined by the presence of distinct antigenic

epitopes.

Denervation increases the number of fibers that express general slow

MyHC, but it decreases the adult slow MyHC epitope. Cross-

reinnervation of slow muscle by a fast nerve leads to an increase in

the number of fibers that express fast MyHC.

In both cases, there is an increase in the number of fibers that

express slow and fast IIA MyHCs, but without the adult slow MyHC

epitope. The data suggest that innervation is required for maturation

and maintenance of diversity of both slow and fast fibers.

The sequence of slow MyHC epitope transitions is a useful biomarker,

and it may play a significant role during nerve-dependent changes in

muscle fiber function.

We applied this detailed muscle analysis to a transgenic mouse model

of human motor and sensory neuropathy IA, also known as Charcot-Marie-

Tooth disease type 1A (CMT1A), in which electrical conduction in some

motor nerves is poor due to demyelination.

The mice display atrophy of some muscle fibers and changes in slow

and fast MyHC epitope expression, suggestive of a progressive

increase in innervation of muscle fibers by fast motor neurons, even

at early stages. The potential role of these early changes in disease

pathogenesis is assessed.