Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis

W. D. Phillips, P. Christadoss, M. Losen, A. R. Punga, K. Shigemoto, J. Verschuuren, A. Vincent

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized.

Original languageEnglish (US)
Pages (from-to)29-40
Number of pages12
JournalExperimental Neurology
Volume270
DOIs
StatePublished - Oct 29 2014

Fingerprint

Myasthenia Gravis
Protein-Tyrosine Kinases
Animal Models
Guidelines
Muscles
Autoantibodies
Neuromuscular Junction
Cholinergic Receptors
Antibodies
Muscle Weakness
Random Allocation
Sample Size
Muscle Cells
Research Design
Therapeutics
Cell Culture Techniques
Immunoglobulin G

Keywords

  • Antibody-mediated
  • Autoantibodies
  • Consensus protocol
  • Experimental design
  • Muscle specific kinase
  • Myasthenia gravis
  • Neuromuscular junction
  • Preclinical
  • Rodent models

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

Cite this

Phillips, W. D., Christadoss, P., Losen, M., Punga, A. R., Shigemoto, K., Verschuuren, J., & Vincent, A. (2014). Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis. Experimental Neurology, 270, 29-40. https://doi.org/10.1016/j.expneurol.2014.12.013

Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis. / Phillips, W. D.; Christadoss, P.; Losen, M.; Punga, A. R.; Shigemoto, K.; Verschuuren, J.; Vincent, A.

In: Experimental Neurology, Vol. 270, 29.10.2014, p. 29-40.

Research output: Contribution to journalArticle

Phillips, WD, Christadoss, P, Losen, M, Punga, AR, Shigemoto, K, Verschuuren, J & Vincent, A 2014, 'Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis', Experimental Neurology, vol. 270, pp. 29-40. https://doi.org/10.1016/j.expneurol.2014.12.013
Phillips WD, Christadoss P, Losen M, Punga AR, Shigemoto K, Verschuuren J et al. Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis. Experimental Neurology. 2014 Oct 29;270:29-40. https://doi.org/10.1016/j.expneurol.2014.12.013
Phillips, W. D. ; Christadoss, P. ; Losen, M. ; Punga, A. R. ; Shigemoto, K. ; Verschuuren, J. ; Vincent, A. / Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis. In: Experimental Neurology. 2014 ; Vol. 270. pp. 29-40.
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