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Updated: Jul 23, 2026
Assessing Functional Performance in the Mdx Mouse Model
Published on: March 27, 2014
Characterization of Alzheimer's disease-like neuropathology in Duchenne's muscular dystrophy using the DBA/2J mdx
Grant C Hayward1, Daniela Caceres2, Emily N Copeland3
1Faculty of Medicine, University of Ottawa, Canada.
Abstract:
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by a mutation in the dystrophin gene. In addition to muscle pathology, some patients with DMD will exhibit cognitive impairments with severity being linked to age and type of genetic mutation. Likewise, some studies have shown that mdx mice display impairments in spatial memory compared with wild-type (WT) controls, while others have not observed any such effect. Most studies have utilized the traditional C57BL/10 (C57) mdx mouse, which exhibits a mild disease phenotype. Recently, the DBA/2J (D2) mdx mouse has emerged as a more severe and perhaps clinically relevant DMD model; however, studies examining cognitive function in these mice are limited. Thus, in this study we examined cognitive function in age-matched C57 and D2 mdx mice along with their respective WT controls. Our findings show that 8- to 12-week-old C57 mdx mice did not display any differences in exploration time when challenged with a novel object recognition test. Conversely, age-matched D2 mdx mice spent less time exploring objects in total as a well as less time exploring the novel object, suggestive of impaired recognition memory. Biochemical analyses of the D2 mdx brain revealed higher soluble amyloid precursor protein β (APPβ) and APP in the prefrontal cortex of mdx mice compared with WT, and lower soluble APPα in the hippocampus, suggestive of a shift towards amyloidogenesis and a similar pathogenesis to Alzheimer's disease. Furthermore, our study demonstrates the utility of the D2 mdx model in studying cognitive impairment.
Insights
The DBA/2J mdx mouse model of Duchenne muscular dystrophy (DMD) shows impaired recognition memory, unlike the C57 mdx model. This suggests potential Alzheimer's-like brain changes in D2 mdx mice, highlighting its utility for studying DMD cognitive deficits.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Duchenne muscular dystrophy (DMD) is a genetic disorder causing muscle wasting.
- Cognitive impairments are observed in some DMD patients, with severity linked to genetic mutations.
- Previous studies on cognitive function in mdx mouse models of DMD have yielded inconsistent results, often using the milder C57BL/10 (C57) strain.
Purpose of the Study:
- To investigate cognitive function in the DBA/2J (D2) mdx mouse model, a potentially more clinically relevant DMD model.
- To compare cognitive performance between D2 mdx mice, C57 mdx mice, and their respective wild-type (WT) controls.
- To explore potential biochemical mechanisms underlying cognitive deficits in D2 mdx mice.
Main Methods:
- Novel object recognition test to assess recognition memory in age-matched C57 and D2 mdx mice and WT controls.
- Biochemical analysis of brain tissue (prefrontal cortex and hippocampus) from D2 mdx mice and WT controls.
- Assessment of soluble amyloid precursor protein beta (APPβ), APP, and soluble APPα levels.
Main Results:
- C57 mdx mice (8-12 weeks old) showed no significant differences in exploration time compared to WT controls.
- D2 mdx mice exhibited impaired recognition memory, spending less time exploring objects, particularly the novel one.
- Biochemical analysis revealed increased APPβ and APP in the prefrontal cortex and decreased soluble APPα in the hippocampus of D2 mdx mice compared to WT.
Conclusions:
- The D2 mdx mouse model displays impaired recognition memory, unlike the C57 mdx model.
- Findings suggest a shift towards amyloidogenesis in the D2 mdx mouse brain, potentially mirroring Alzheimer's disease pathogenesis.
- The D2 mdx mouse is a valuable model for studying cognitive impairments associated with Duchenne muscular dystrophy.
