Format

Send to

Choose Destination
PLoS One. 2016 Mar 15;11(3):e0151467. doi: 10.1371/journal.pone.0151467. eCollection 2016.

High Frequency Hearing Loss and Hyperactivity in DUX4 Transgenic Mice.

Author information

1
Lillehei Heart Institute and Department of Pediatrics, University of Minnesota, Minneapolis, 55455, United States of America.
2
Department of Biochemistry, University of Minnesota, Minneapolis, 55455, United States of America.
3
Program in Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, 55455, United States of America.
4
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, 55455, United States of America.

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is caused by mutations leading to ectopic expression of the transcription factor DUX4, and encompasses both muscle-related and non-muscle phenotypes. Mouse models bearing this gene represent valuable tools to investigate which pathologies are due to DUX4 expression, and how DUX4 leads to these pathologies. The iDUX4(2.7) mouse contains an X-linked doxycycline-inducible DUX4 gene that shows low level basal expression in the absence of doxycycline, leading to male lethality, generally in embryo, but always before 8 weeks of age. Here, we describe additional non-muscle phenotypes in this animal model. We find that iDUX4(2.7) female carriers are extremely hyperactive, spending large amounts of time ambulating and much less time resting. Rare 3-week old males, although hypophagic, runted and extremely fragile, are capable of high activity, but show periods of catatonic torpor in which animals appear dead and respiration is virtually absent. We also examine a non-muscle phenotype of interest to FSHD, high frequency hearing loss. We find that young iDUX4(2.7) females are significantly impaired in their ability to hear at frequencies above 8 kHz. These phenotypes make the iDUX4(2.7) mouse an attractive model in which to study non-muscle activities of DUX4.

PMID:
26978271
PMCID:
PMC4792399
DOI:
10.1371/journal.pone.0151467
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center