In Vivo Non-invasive Monitoring of Dystrophin Correction in a New Duchenne Muscular Dystrophy Reporter Mouse

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Oct 6

PMID 31586095

Citations 22

Authors

Leonela Amoasii

Hui Li

Yu Zhang

Yi-Li Min

Efrain Sanchez-Ortiz

John M Shelton

Chengzu Long

Alex A Mireault

Samadrita Bhattacharyya

John R McAnally

Rhonda Bassel-Duby

Eric N Olson

Affiliations

Soon will be listed here.

Abstract

Duchenne muscular dystrophy (DMD) is a fatal genetic disorder caused by mutations in the dystrophin gene. To enable the non-invasive analysis of DMD gene correction strategies in vivo, we introduced a luciferase reporter in-frame with the C-terminus of the dystrophin gene in mice. Expression of this reporter mimics endogenous dystrophin expression and DMD mutations that disrupt the dystrophin open reading frame extinguish luciferase expression. We evaluated the correction of the dystrophin reading frame coupled to luciferase in mice lacking exon 50, a common mutational hotspot, after delivery of CRISPR/Cas9 gene editing machinery with adeno-associated virus. Bioluminescence monitoring revealed efficient and rapid restoration of dystrophin protein expression in affected skeletal muscles and the heart. Our results provide a sensitive non-invasive means of monitoring dystrophin correction in mouse models of DMD and offer a platform for testing different strategies for amelioration of DMD pathogenesis.

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