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Updated: May 1, 2026
Echocardiographic Assessment of the Right Heart in Mice
Published on: November 27, 2013
Right ventricular dysfunction in the R6/2 transgenic mouse model of Huntington's disease is unmasked by dobutamine
Guido Buonincontri1, Nigel I Wood2, Simon G Puttick2
1Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK, CB2 0QQ.
Insights
Right ventricle (RV) dysfunction worsens with age in the R6/2 mouse model of Huntington's disease (HD). This RV impairment occurs before symptoms appear, highlighting cardiovascular dysfunction as a key aspect of HD.
Area of Science:
- Cardiovascular Research
- Neurodegenerative Diseases
- Animal Models
Background:
- Cardiovascular dysfunction is increasingly recognized in Huntington's disease (HD).
- Previous studies in the R6/2 mouse model noted left ventricular abnormalities but preserved systolic function.
- Ventricular interdependence suggests right ventricle (RV) dysfunction may contribute to HD cardiac pathology.
Purpose of the Study:
- To investigate RV function in the R6/2 mouse model of HD.
- To assess RV functional changes throughout disease progression.
- To evaluate RV response to beta-adrenergic stress in early-stage HD.
Main Methods:
- Cardiac cine-magnetic resonance imaging (MRI) was employed to assess RV functional parameters.
- Longitudinal imaging tracked RV function changes with disease progression in R6/2 mice.
- Dobutamine stress tests compared RV response in wildtype and early-symptomatic R6/2 mice.
Main Results:
- Progressive deterioration of RV systolic function was observed with increasing age in R6/2 mice.
- RV dysfunction was detected in R6/2 mice under dobutamine stimulation prior to overt disease symptoms.
- This indicates early-onset cardiac impairment in the HD model.
Conclusions:
- This study demonstrates, for the first time, the involvement of the right ventricle in cardiovascular dysfunction in the R6/2 HD mouse model.
- Progressive RV dysfunction occurs in this model, preceding clinical manifestation.
- Cardiovascular dysfunction, specifically RV involvement, should be considered in HD therapeutic strategies and biomarker development.
Background:
Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence.
Objective:
To investigate RV function in the R6/2 mouse model of Huntington's disease (HD).
Methods:
Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice.
Results:
There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent.
Conclusions:
This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.
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