PMID- 28823823
OWN - NLM
STAT- MEDLINE
DCOM- 20171005
LR  - 20180404
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 297
DP  - 2017 Nov
TI  - Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated 
      myasthenia gravis.
PG  - 158-167
LID - S0014-4886(17)30211-X [pii]
LID - 10.1016/j.expneurol.2017.08.006 [doi]
AB  - Since the first report of experimental animal models of myasthenia gravis (MG) 
      with autoantibodies against low-density lipoprotein receptor-related protein 4 
      (LRP4), there have not been any major reports replicating the pathogenicity of 
      anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the 
      specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the 
      need for further research. In this study, we purified antigens corresponding to 
      the extracellular region of human LRP4 stably expressed with chaperones in 293 
      cells and used these antigens to immunize female A/J mice. Immunization with LRP4 
      protein caused mice to develop myasthenia having similar electrophysiological and 
      histological features as are observed in MG patients with circulating Abs against 
      muscle-specific kinase (MuSK). Our results clearly demonstrate that active 
      immunization of mice with LRP4 proteins causes myasthenia similar to the MG 
      induced by anti-MuSK Abs. Further experimental and clinical studies are required 
      to prove the pathogenicity of anti-LRP4 Abs in MG patients.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Mori, Shuuichi
AU  - Mori S
AD  - Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 
      Tokyo, Japan.
FAU - Motohashi, Norio
AU  - Motohashi N
AD  - Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 
      Tokyo, Japan.
FAU - Takashima, Rumi
AU  - Takashima R
AD  - Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 
      Tokyo, Japan.
FAU - Kishi, Masahiko
AU  - Kishi M
AD  - Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, 
      Japan.
FAU - Nishimune, Hiroshi
AU  - Nishimune H
AD  - Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 
      Kansas City, KS, United States.
FAU - Shigemoto, Kazuhiro
AU  - Shigemoto K
AD  - Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 
      Tokyo, Japan. Electronic address: kazshige@tmig.or.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170818
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (LRP4 protein, human)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Immunization/*adverse effects/methods
MH  - LDL-Receptor Related Proteins/administration & dosage/*toxicity
MH  - Mice
MH  - Muscle Weakness/chemically induced/metabolism/physiopathology
MH  - Myasthenia Gravis/*chemically induced/*metabolism/physiopathology
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
OTO - NOTNLM
OT  - Animal model
OT  - Lrp4
OT  - MuSK
OT  - Myasthenia gravis
OT  - Neuromuscular junction
EDAT- 2017/08/22 06:00
MHDA- 2017/10/06 06:00
CRDT- 2017/08/22 06:00
PHST- 2017/06/27 00:00 [received]
PHST- 2017/08/11 00:00 [revised]
PHST- 2017/08/11 00:00 [accepted]
PHST- 2017/08/22 06:00 [pubmed]
PHST- 2017/10/06 06:00 [medline]
PHST- 2017/08/22 06:00 [entrez]
AID - S0014-4886(17)30211-X [pii]
AID - 10.1016/j.expneurol.2017.08.006 [doi]
PST - ppublish
SO  - Exp Neurol. 2017 Nov;297:158-167. doi: 10.1016/j.expneurol.2017.08.006. Epub 2017 
      Aug 18.