High frequency hearing loss and hyperactivity in DUX4 transgenic mice

Abhijit Dandapat, Benjamin J. Perrin, Christine Cabelka, Maria Razzoli, James M. Ervasti, Alessandro Bartolomucci, Dawn A. Lowe, Michael Kyba

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0151467
JournalPloS one
Volume11
Issue number3
DOIs
StatePublished - Mar 2016

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High-Frequency Hearing Loss
Audition
hearing
Transgenic Mice
Doxycycline
Facioscapulohumeral Muscular Dystrophy
genetically modified organisms
Pathology
Phenotype
phenotype
muscular dystrophy
doxycycline
animal models
mice
Animals
Bearings (structural)
Genes
Torpor
Muscle
resting periods

Cite this

High frequency hearing loss and hyperactivity in DUX4 transgenic mice. / Dandapat, Abhijit; Perrin, Benjamin J.; Cabelka, Christine; Razzoli, Maria; Ervasti, James M.; Bartolomucci, Alessandro; Lowe, Dawn A.; Kyba, Michael.

In: PloS one, Vol. 11, No. 3, e0151467, 03.2016.

Research output: Contribution to journalArticle

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