Animal Models of Muscular Dystrophy

Abstract

The muscular dystrophies (MDs) represent a diverse collection of inherited human disorders, which affect to varying degrees skeletal, cardiac, and sometimes smooth muscle (Emery, 20021). To date, more than 50 different genes have been implicated as causing one or more types of MD (Bansal et al., 20032). In many cases, invaluable insights into disease mechanisms, structure and function of gene products, and approaches for therapeutic interventions have benefited from the study of animal models of the different MDs (Arnett et al., 20093). The large number of genes that are associated with MD and the tremendous number of animal models that have been developed preclude a complete discussion of each in the context of this review. However, we summarize here a number of the more commonly used models together with a mixture of different types of gene and MD, which serves to give a general overview of the value of animal models of MD for research and therapeutic development.

Exome sequencing reveals independent SGCD deletions causing limb girdle muscular dystrophy in Boston terriers

“…To date, only small animal models are available for study: gene-targeted mouse models for α-, β-, δ-, and γ-sarcoglycanopathy [27] and a spontaneous hamster model for δ-sarcoglycanopathy [28,29]. Here, we have demonstrated that a naturally occurring muscular dystrophy in a Boston terrier family is a sarcoglycanopathy, consistent with two previously published case reports in the breed.…”

Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

“…Although transgenic models involving higher mammals have breeding and ethical issues (49), transgenic mice are limited by stringent maintenance, restricted ability to recapitulate the human pathology, and species-related variations. For example, the mdx mouse model of DMD displays moderate pathology limited to early stages, predominantly in the diaphragm muscle (8). This is in contrast to the fast progressive pathogenesis in different skeletal muscles, worsening symptoms, and reduced lifespan in DMD patients.…”

“…The limited therapeutic option for muscle pathologies has necessitated the investigation of the underlying mechanisms employing various experimental models (8,48). However, a single model that meticulously mimics all the features of MD and IMs is non-existent (2).…”

“…Altered reduced/oxidized markers has been reported in MD patients and animal models (7,8,13,81). ROS produced in mdx mice and Col6a1 Ϫ/Ϫ mice might contribute to muscle pathology (80).…”

“…MDs have been extensively studied using patient muscle biopsies (6,7) and genetic models (8). However, the models do not replicate the human condition due to species barrier, altered chronology of events, and variable severity of muscle pathology (2).…”