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Social and emotional alterations in mice lacking the short dystrophin-gene product, Dp71
Rubén Miranda1,2, Léa Ceschi3, Delphine Le Verger3
1Université Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay, 91400, Saclay, France. rubenmir@ucm.es.
Background:
The Duchenne and Becker muscular dystrophies (DMD, BMD) are neuromuscular disorders commonly associated with diverse cognitive and behavioral comorbidities. Genotype-phenotype studies suggest that severity and risk of central defects in DMD patients increase with cumulative loss of different dystrophins produced in CNS from independent promoters of the DMD gene. Mutations affecting all dystrophins are nevertheless rare and therefore the clinical evidence on the contribution of the shortest Dp71 isoform to cognitive and behavioral dysfunctions is limited. In this study, we evaluated social, emotional and locomotor functions, and fear-related learning in the Dp71-null mouse model specifically lacking this short dystrophin.
Results:
We demonstrate the presence of abnormal social behavior and ultrasonic vocalization in Dp71-null mice, accompanied by slight changes in exploratory activity and anxiety-related behaviors, in the absence of myopathy and alterations of learning and memory of aversive cue-outcome associations.
Conclusions:
These results support the hypothesis that distal DMD gene mutations affecting Dp71 may contribute to the emergence of social and emotional problems that may relate to the autistic traits and executive dysfunctions reported in DMD. The present alterations in Dp71-null mice may possibly add to the subtle social behavior problems previously associated with the loss of the Dp427 dystrophin, in line with the current hypothesis that risk and severity of behavioral problems in patients increase with cumulative loss of several brain dystrophin isoforms.
Insights
Duchenne and Becker muscular dystrophies (DMD, BMD) are linked to cognitive and behavioral issues. Loss of the Dp71 dystrophin isoform in mice caused social and emotional deficits, suggesting its role in DMD-related behavioral problems.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Duchenne and Becker muscular dystrophies (DMD, BMD) are neuromuscular disorders with associated cognitive and behavioral comorbidities.
- Central nervous system (CNS) defects in DMD patients correlate with cumulative loss of dystrophin isoforms.
- Clinical data on the contribution of the Dp71 isoform to cognitive and behavioral dysfunction is limited due to the rarity of mutations affecting all dystrophins.
Purpose of the Study:
- To investigate the role of the Dp71 dystrophin isoform in social, emotional, locomotor, and fear-related learning functions.
- To evaluate the behavioral phenotype of a Dp71-null mouse model lacking this specific short dystrophin.
Main Methods:
- Utilized a Dp71-null mouse model specifically engineered to lack the Dp71 dystrophin isoform.
- Assessed social behavior, ultrasonic vocalization, exploratory activity, anxiety-related behaviors, and fear-related learning in Dp71-null mice.
- Examined for the presence of myopathy and alterations in learning and memory.
Main Results:
- Dp71-null mice exhibited abnormal social behavior and ultrasonic vocalization.
- Slight alterations in exploratory activity and anxiety-related behaviors were observed.
- No myopathy or significant alterations in learning and memory of aversive cue-outcome associations were detected.
Conclusions:
- The findings support the hypothesis that mutations affecting Dp71 contribute to social and emotional problems in DMD, potentially relating to autistic traits and executive dysfunction.
- The observed alterations in Dp71-null mice may exacerbate social behavior issues previously linked to Dp427 loss.
- This research aligns with the theory that cumulative loss of brain dystrophin isoforms increases the risk and severity of behavioral problems in DMD patients.
