A Panel of Slow-Channel Syndrome Mice Reveals a Unique Locomotor Behavioral Signature

Article type: Brief Report

Authors: Grajales-Reyes, José G.^{a; 1; 2} | García-González, Aurian^{a; 1; 3} | María-Ríos, José C.^{a; 4} | Grajales-Reyes, Gary E.^{a; 2} | Delgado-Vélez, Manuel^{a; 5} | Báez-Pagán, Carlos A.^{a; 6} | Quesada, Orestes^c | Gómez, Christopher M.^d | Lasalde-Dominicci, José A.^{a; b; 5; *}

Affiliations: [a] Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, PR, USA | [b] Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, PR, USA | [c] Department of Physical Sciences, University of Puerto Rico, Río Piedras Campus, San Juan, PR, USA | [d] Department of Neurology, The University of Chicago, Chicago, IL, USA

Correspondence: [*] Correspondence to: J.A. Lasalde-Dominicci, Department of Biology, University of Puerto Rico, Río Piedras Campus, PO Box 23360, San Juan, PR 00931, USA. E-mail: [email protected].

Note: [1] Indicates equal contributions in this publication.

Note: [2] Present address: Washington University School of Medicine in St Louis, Medical Scientist Training Program (MSTP), MSTP-Box 8226, 660 Euclid Avenue, St. Louis, MO 63110-1093.

Note: [3] Present address: University of Massachusetts Medical School, Medical Scientist Training Program (MSTP), 55 Lake Ave North Worcester, Massachusetts 01655-0116.

Note: [4] Present address: University of Puerto Rico, Medical Sciences Campus, Box 365067, San Juan, PR 00936-5067.

Note: [5] Present address: Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926.

Note: [6] Present address: University of Puerto Rico, Physical Sciences Department, P.O. BOX 23323, San Juan PR. 00931-3323.

Abstract: Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel syndrome (SCS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ɛL269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours. Our approach suggests a robust relationship between the pathophysiology of SCS and locomotor activity.

Keywords: Congenital myasthenia, acetylcholine, motor endplate, myalgia, running, locomotor activity, mice, nicotinic acetylcholine receptor (nAChR), neuromuscular junction (NMJ)

DOI: 10.3233/JND-170226

Journal: Journal of Neuromuscular Diseases, vol. 4, no. 4, pp. 341-347, 2017