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Aberrant expression of DUX4, a gene unique to humans and primates, causes Facioscapulohumeral Muscular Dystrophy-1 (FSHD), yet the pathogenic mechanism is unknown. As transgenic overexpression models have largely failed to replicate the genetic changes seen in FSHD, many studies of endogenously expressed DUX4 have been limited to patient biopsies and myogenic cell cultures, which never fully differentiate into mature muscle fibers. We have developed a method to xenograft immortalized human muscle precursor cells from patients with FSHD and first-degree relative controls into the tibialis anterior muscle compartment of immunodeficient mice, generating human muscle xenografts. We report that FSHD cells mature into organized and innervated human muscle fibers with minimal contamination of murine myonuclei. They also reconstitute the satellite cell niche within the xenografts. FSHD xenografts express DUX4 and DUX4 downstream targets, retain the 4q35 epigenetic signature of their original donors, and express a novel protein biomarker of FSHD, SLC34A2. Ours is the first scalable, mature in vivo human model of FSHD. It should be useful for studies of the pathogenic mechanism of the disease as well as for testing therapeutic strategies targeting DUX4 expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although several noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to be substantially efficacious in experimental models of brain trauma, side effects associated with this class of compounds have impeded clinical application. Therefore, new noncompetitive NMDA receptor antagonists have been developed, including NPS 1506, that appear to be nontoxic but retain efficacy. In the present study, we evaluated the efficacy of NPS 1506 in a model of parasagittal fluid percussion brain trauma in the anesthetized rat. Administration of 1 mg/kg NPS 1506 at both 10 min and 4 h posttrauma induced no changes in brain temperature, mean arterial pressure, pulse, or arterial blood gasses. At 1 week postinjury, animals treated with the same dosing regimen of NPS 1506 demonstrated a dramatic attenuation of memory dysfunction evaluated by a water maze task (P < 0.02) and had greatly reduced neuron death in the CA3 subfield of the hippocampus (P < 0.01). However, NPS 1506 treatment did not significantly affect the extent of cortical tissue loss following injury. Since memory dysfunction and hippocampal damage are common and potentially related consequences of brain trauma in humans, our results suggest that NPS 1506 treatment may have clinical utility., (Copyright 2000 Academic Press.)