PT  - JOURNAL ARTICLE
AU  - Bai, Yunhong
AU  - Pisciotta, Chiara
AU  - Wang, Suola
AU  - Wu, Xingyao
AU  - Schwab, Markus H
AU  - Nave, Klaus Armin
AU  - Shy, Michael
TI  - Three-Dimensional Study of Neuromuscular Junctions (NMJ) in Heterozygous R98C Knock-in CMT1B Mouse Model by Overexpression Neuregulin 1 Type III (S44.005)
DP  - 2016 Apr 05
TA  - Neurology
PG  - S44.005
VI  - 86
IP  - 16 Supplement
4099  - http://n.neurology.org/content/86/16_Supplement/S44.005.short
4100  - http://n.neurology.org/content/86/16_Supplement/S44.005.full
SO  - Neurology2016 Apr 05; 86
AB  - OBJECTIVE: By crossing myelin protein zero (MPZ) R98C/+ heterozygous mice with transgenic mice that over-express HA-Neuregulin 1 type III (Nrg1*, HANI), our goal is to investigate whether improved myelination and increased thickness of myelin is observed. BACKGROUND: R98C mutation in myelin protein zero (MPZ) results in an early-onset and severe form of Charcot-Marie-Tooth disease 1B (CMT1B). This neuropathy is similarly observed in knock-in mice. Prior experiments revealed Nrg1* signaling from axons will bind to ErbB2/3 tyrosine kinase receptors on myelinating Schwann cells, initiating signaling pathways that regulate myelin thickness. Overexpression of Nrg1* in HANI mice have resulted in increased myelin thickness in peripheral nerve axons. Nrg1* has been hypothesized to also facilitate cell-cell interactions at NMJ. DESIGN/METHODS: R98C mice and HANI mice were crossed. Offspring were first genotyped to identify transgene (Nrg1*) presence in R98C MPZ mice and then evaluated clinically, physiologically and morphologically via 3D reconstruction of NMJs. Relevant protein expressions were analyzed via western blot and immunohistochemistry. RESULTS: Increased myelin thickness and reduced G-ratios were observed in HANI/+/R98C/+. Nerve terminal pattern differences revealed increased presence of NMJ with nerve terminal “Boutons” in addition to increased density of acetylcholine receptors of NMJ in HANI/+/R98C/+ as compared statistically to R98C/+ mice. 3D reconstruction of NMJs observed from shadow, transparence, and surface displayed presynaptic nerve terminals having taken on a spherical and enlarged shape in the HANI/+/R98C/+ mice. CONCLUSIONS: Increasing Nrg1* expression induced mild increases in myelin thickness and affected nerve terminal morphology of NMJ, but did not rescue the clinical, physiological or molecular features of the R98C MPZ model of CMT1B. Supported by: Muscular Dystrophy Association, NINDS.Disclosure: Dr. Bai has nothing to disclose. Dr. Pisciotta has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Schwab has nothing to disclose. Dr. Nave has nothing to disclose. Dr. Shy has nothing to disclose.Thursday, April 21 2016, 6:30 am-8:30 am