May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
DOK-7 Expression at the Neuromuscular Junction of Extraocular Muscle
Author Affiliations & Notes
  • L. L. Kusner
    Saint Louis University, St Louis, Missouri
  • D. Liu
    Saint Louis University, St Louis, Missouri
    Neurology and Psychiatry,
  • B. Gong
    Saint Louis University, St Louis, Missouri
    Neurology and Psychiatry,
  • Footnotes
    Commercial Relationships  L.L. Kusner, None; D. Liu, None; B. Gong, None.
  • Footnotes
    Support  RPB Challenge Grant, National Eye Institute EY-015306 and EY14837
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4119. doi:
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      L. L. Kusner, D. Liu, B. Gong; DOK-7 Expression at the Neuromuscular Junction of Extraocular Muscle. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4119. doi:

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Congenital myasthenic syndromes are genetic disorders caused by mutations in genes critical for effective neuromuscular transmission. Mutations in Dok7, which is involved in clustering of acetylcholine receptor, have been identified. These individuals have a distinct phenotype of a limb-girdle distribution of weakness with some ptosis but sparing of eye movements, which differentiates the patients from typical neuromuscular transmission disorder patients who have preferential involvement of extraocular muscles. The purpose of the study was to determine if DOK-7 plays a role at the neuromuscular junction of extraocular muscle (EOM).

Methods: : Microarray analysis was performed on EOM, diaphragm, tibialis anterior, and quadriceps. Real time PCR was performed to confirm results of RNA expression levels of DOK-7. Neuromuscular junctions of EOM, tibialis anterior, EDL and diaphragm were assessed for localization of DOK-7 protein by immunohistochemistry using DOK-7 antibody and visualized through the use of Oregon Green conjugated anti-rabbit IgG. Neuromuscular junctions were identified by bungarotoxin conjugated to Alexa 488.

Results: : The microarray analysis showed that EOM and quadriceps had the highest expression level. Tibialis anterior and diaphragm had the lowest level of expression. The real time PCR confirmed these results. Looking at the expression of protein by immunohistochemistry, EDL demonstrated a strong staining pattern whereas; the intensity of DOK-7 staining of diaphragm was markedly less. EOM staining by the DOK-7 antibody showed a variation in the staining of endplates, although both single innervated and multi-innervated junctions showed immunoreactivity. The orbital region contained NMJ which stained less intensely than that of the global region.

Conclusions: : EOM NMJ contains DOK-7 protein that functions to cluster the acetylcholine receptor. The variation in the protein level may relate to level of acetylcholine receptor expression. The resulting expression of DOK-7 at the NMJ does not explain the identifiable lack of weakness of the EOM in the Congenital myasthenic with the Dok7 mutations. It is possible that EOM junctions may have additional mechanisms that support clustering of acetylcholine receptors to the postsynaptic region in the absence of Dok7.

Keywords: extraocular muscles: structure • synapse • immunohistochemistry 

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