| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 The Institute for Biomedical Sciences, George Washington University, Washinton, DC, USA; Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA
2 Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: Ehoffman{at}cnmcresearch.org.
Abstract
The neuromuscular junction (NMJ) is a regionally specialized area of myofibers, and is defined, in part, by specific gene expression from underlying myonuclei. We sought to obtain a more complete picture of the mRNA transcripts and proteins playing a role in NMJ formation and maintenance using laser capture microdissection (LCM) and to define the expression profiles of the nuclear domain at the NMJ. NMJs (800) were isolated from normal mouse tibialis anterior (TA) muscle by LCM, with an equal amount of adjacent non-NMJ regions isolated. Many known components of the NMJ were found significantly differentially expressed. Three differentially expressed, potential novel components of the NMJ were chosen for further study, and each was validated by immunostaining with and without blocking peptides (3/3), quantitative RT-PCR (3/3), and in situ hybridization (1/3). The three genes that were validated were DUSP6 (dual specificity phosphatase), RRBP1 (ribosomal receptor binding protein), and VPS26 (vacuolar protein sorting). Query of each of these novel components in a 27 time point in vivo muscle regeneration series showed expression commensurate with previously known NMJ markers (nestin, 
-AChR). All data is publicly accessible, and can be queried via web Oracle graphical interfaces to determine the relative expression of any gene in NMJ versus non-NMJ nuclear domains. Understanding and discovering the elements responsible for the integrity and the function of the NMJs is of relevance to understanding neuromuscular disease such as spinal muscular atrophy. Our LCM-based mRNA expression profiling has provided us with new means of identification of specific genes potentially responsible for NMJ stability and function and new candidates for involvement in disease pathogenesis.
This article has been cited by other articles:
|
|
 |
|
  R G E van Eijsden, L M T Eijssen, P J Lindsey, C M M van den Burg, L E A de Wit, M E Rubio-Gozalbo, C E M de Die, T Ayoubi, W Sluiter, I F M de Coo, et al. Termination of damaged protein repair defines the occurrence of symptoms in carriers of the m.3243A>G tRNALeu mutation J. Med. Genet., August 1, 2008; 45(8): 525 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Perkins, U. Basu, M. T. Budak, C. Ketterer, S. M. Baby, O. Lozynska, J. A. Lunde, B. J. Jasmin, N. A. Rubinstein, and T. S. Khurana Ets-2 Repressor Factor Silences Extrasynaptic Utrophin by N-Box mediated Repression in Skeletal Muscle Mol. Biol. Cell, August 1, 2007; 18(8): 2864 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kang, L. Tian, Y.-J. Son, Y. Zuo, D. Procaccino, F. Love, C. Hayworth, J. Trachtenberg, M. Mikesh, L. Sutton, et al. Regulation of the Intermediate Filament Protein Nestin at Rodent Neuromuscular Junctions by Innervation and Activity J. Neurosci., May 30, 2007; 27(22): 5948 - 5957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fraterman, T. S. Khurana, and N. A. Rubinstein Identification of acetylcholine receptor subunits differentially expressed in singly and multiply innervated fibers of extraocular muscles. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3828 - 3834. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
