PMID- 16697051 OWN - NLM STAT- MEDLINE DCOM- 20060726 LR - 20161124 IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 175 IP - 1-2 DP - 2006 Jun TI - Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK). PG - 107-17 AB - Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes. CONCLUSION: Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway. FAU - Jha, Smita AU - Jha S AD - Department of Biology and Biochemistry, University of Houston, TX 77204, USA. FAU - Xu, Kaiping AU - Xu K FAU - Maruta, Takahiro AU - Maruta T FAU - Oshima, Minako AU - Oshima M FAU - Mosier, Dennis R AU - Mosier DR FAU - Atassi, M Zouhair AU - Atassi MZ FAU - Hoch, Werner AU - Hoch W LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060511 PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Autoantibodies) RN - 0 (Receptors, Cholinergic) RN - 0 (Recombinant Proteins) RN - EC 2.7.10.1 (MuSK protein, rat) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Action Potentials/immunology MH - Animals MH - Autoantibodies/biosynthesis/blood MH - Cells, Cultured MH - Cricetinae MH - Extracellular Fluid/*enzymology/immunology MH - Female MH - Immunization MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Muscle, Skeletal/immunology/metabolism MH - Myasthenia Gravis/*enzymology/*immunology MH - Protein Structure, Tertiary MH - Rats MH - Receptor Protein-Tyrosine Kinases/*administration & dosage/*immunology MH - Receptors, Cholinergic/*administration & dosage/*immunology MH - Recombinant Proteins/administration & dosage/immunology EDAT- 2006/05/16 09:00 MHDA- 2006/07/27 09:00 CRDT- 2006/05/16 09:00 PHST- 2005/12/01 00:00 [received] PHST- 2006/02/08 00:00 [revised] PHST- 2006/03/10 00:00 [accepted] PHST- 2006/05/16 09:00 [pubmed] PHST- 2006/07/27 09:00 [medline] PHST- 2006/05/16 09:00 [entrez] AID - S0165-5728(06)00086-5 [pii] AID - 10.1016/j.jneuroim.2006.03.016 [doi] PST - ppublish SO - J Neuroimmunol. 2006 Jun;175(1-2):107-17. doi: 10.1016/j.jneuroim.2006.03.016. Epub 2006 May 11.