Related Experiment Video
Updated: Aug 11, 2026
In utero Measurement of Heart Rate in Mouse by Noninvasive M-mode Echocardiography
Published on: November 22, 2013
Electrocardiographic and other cardiac anomalies in beta-glucuronidase-null mice corrected by nonablative neonatal
A J T Schuldt1, T J Hampton, V Chu
1The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Insights
Neonatal bone marrow transplantation prevents severe cardiac disease in a mouse model of lysosomal storage disease (LSD). This approach offers a promising, non-toxic treatment for preventing cardiovascular issues in patients with mucopolysaccharidosis type VII.
Area of Science:
- Biomedical Science
- Genetics
- Cardiology
Background:
- Lysosomal storage diseases (LSDs) cause significant cardiovascular problems, often treated with risky interventions.
- Current therapies like valve replacement and bone marrow transplantation carry high risks for debilitated patients.
- Enzyme replacement therapy shows limited long-term efficacy for cardiac LSD.
Purpose of the Study:
- To investigate the efficacy of early, non-myeloablative bone marrow (BM) transplantation in preventing cardiac manifestations of LSD.
- To evaluate the long-term engraftment and therapeutic effects of BM transplantation in a mouse model of mucopolysaccharidosis type VII (MPSVII).
Main Methods:
- Utilized beta-glucuronidase (GUSB) null mice, a model for MPSVII (Sly syndrome).
- Administered intravenous BM transplantation to neonatal MPSVII mice without myeloablative pretreatment.
- Assessed GUSB+ donor cell presence, enzyme levels, cardiac function via electrocardiography, and tissue storage post-transplantation.
Main Results:
- BM recipients showed sustained GUSB+ donor cell engraftment in blood and heart up to 11 months.
- Significantly reduced beta-hexosamindase levels in treated MPSVII hearts (P = 0.001).
- Normalized heart rate, PR, PQ, and QRS intervals; reduced tissue storage in various cardiac structures; normalized heart/body weight ratio.
Conclusions:
- Neonatal BM transplantation without toxic pretreatment can prevent severe cardiovascular manifestations in MPSVII mice.
- This strategy offers a potential therapeutic avenue for LSD, mitigating life-threatening cardiac complications.
- Further research is needed to understand the mechanisms behind ECG normalization despite residual myocyte storage.
Abstract:
Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantile-onset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in beta-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at > or = 11 months of age. The enzyme beta-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (P = 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart/body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.
