PMID- 34228850
OWN - NLM
STAT- MEDLINE
DCOM- 20210910
LR  - 20210929
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 54
IP  - 4
DP  - 2021 Aug
TI  - Timing and localization of myasthenia gravis-related gene expression.
PG  - 5574-5585
LID - 10.1111/ejn.15382 [doi]
AB  - Myasthenia gravis (MG) is an acquired autoimmune disorder caused by 
      autoantibodies binding acetylcholine receptors (AChR), muscle-specific kinase 
      (MuSK), agrin or low-density lipoprotein receptor-related protein 4 (Lrp4). These 
      autoantibodies inhibit neuromuscular transmission by blocking the function of 
      these proteins and thereby cause fluctuating skeletal muscle weakness. Several 
      reports suggest that these autoantibodies might also affect the central nervous 
      system (CNS) in MG patients. A comprehensive overview of the timing and 
      localization of the expression of MG-related antigens in other organs is 
      currently lacking. To investigate the spatio-temporal expression of MG-related 
      genes outside skeletal muscle, we used in silico tools to assess public 
      expression databases. Acetylcholine esterase, nicotinic AChR alpha1 subunit, agrin, 
      collagen Q, downstream of kinase-7, Lrp4, MuSK and rapsyn were included as 
      MG-related genes because of their well-known involvement in either congenital or 
      autoimmune MG. We investigated expression of MG-related genes in (1) all human 
      tissues using GTEx data, (2) specific brain regions, (3) neurodevelopmental 
      stages, and (4) cell types using datasets from the Allen Institute for Brain 
      Sciences. MG-related genes show heterogenous spatio-temporal expression patterns 
      in the human body as well as in the CNS. For each of these genes, several (new) 
      tissues, brain areas and cortical cell types with (relatively) high expression 
      were identified suggesting a potential role for these genes outside skeletal 
      muscle. The possible presence of MG-related antigens outside skeletal muscle 
      suggests that autoimmune MG, congenital MG or treatments targeting the same 
      proteins may affect MG-related protein function in other organs.
CI  - (c) 2021 The Authors. European Journal of Neuroscience published by Federation of 
      European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Vergoossen, Dana L E
AU  - Vergoossen DLE
AUID- ORCID: 0000-0002-7268-9818
AD  - Department of Human Genetics, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Keo, Arlin
AU  - Keo A
AUID- ORCID: 0000-0002-7501-1033
AD  - Leiden Computational Biology Center, Leiden University Medical Center, Leiden, 
      The Netherlands.
AD  - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
FAU - Mahfouz, Ahmed
AU  - Mahfouz A
AUID- ORCID: 0000-0001-8601-2149
AD  - Department of Human Genetics, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Leiden Computational Biology Center, Leiden University Medical Center, Leiden, 
      The Netherlands.
AD  - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
FAU - Huijbers, Maartje G
AU  - Huijbers MG
AUID- ORCID: 0000-0002-6082-5042
AD  - Department of Human Genetics, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Department of Neurology, Leiden University Medical Center, Leiden, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210720
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Agrin)
RN  - 0 (Autoantibodies)
RN  - 0 (LDL-Receptor Related Proteins)
SB  - IM
MH  - Agrin
MH  - Autoantibodies
MH  - Gene Expression
MH  - Humans
MH  - *LDL-Receptor Related Proteins
MH  - *Myasthenia Gravis/genetics
PMC - PMC8457065
OTO - NOTNLM
OT  - Dok7
OT  - Lrp4
OT  - MuSK
OT  - brain
OT  - myasthenia gravis
OT  - neuromuscular junction
COIS- LUMC receives royalties from IBL for a MuSK diagnostic assay. LUMC and MGH 
      receive royalties from licensed patent applications on MuSK-related research. The 
      other authors report no conflict of interests.
EDAT- 2021/07/07 06:00
MHDA- 2021/09/11 06:00
PMCR- 2021/09/22
CRDT- 2021/07/06 17:28
PHST- 2021/06/01 00:00 [revised]
PHST- 2021/03/26 00:00 [received]
PHST- 2021/07/01 00:00 [accepted]
PHST- 2021/07/07 06:00 [pubmed]
PHST- 2021/09/11 06:00 [medline]
PHST- 2021/07/06 17:28 [entrez]
PHST- 2021/09/22 00:00 [pmc-release]
AID - EJN15382 [pii]
AID - 10.1111/ejn.15382 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2021 Aug;54(4):5574-5585. doi: 10.1111/ejn.15382. Epub 2021 Jul 
      20.