Related Experiment Videos
Syngeneic bone marrow transplantation reduces the hearing loss associated with murine mucopolysaccharidosis type VII
M S Sands1, L C Erway, C Vogler
1Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
MPS VII mice are deficient in beta-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VII (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage in many organs of the MPS VII mouse. In this report, we quantify the hearing loss and determine the impact of syngeneic BMT on the development of deafness and the associated pathology in the MPS VII mouse. Eleven weeks after syngeneic BMT performed at birth, treated MPS VII mice had normal auditory-evoked brainstem responses (ABR), whereas untreated MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bone and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle ear mucosa and decreased distortion of the ossicles and the cochlear bone. Although transplanted MPS VII mice had increased ABR thresholds by 33 weeks of age, four of the six had thresholds 12 to 32 dB lower than untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, results in long-term improved auditory function.
Insights
Syngeneic bone marrow transplantation (BMT) in newborn mice with mucopolysaccharidosis type VII (MPS VII) prevents early hearing loss. This treatment also improved auditory function long-term in some mice, offering hope for treating hearing impairment in MPS VII.
Area of Science:
- Genetics and Genetic Disorders
- Otolaryngology
- Regenerative Medicine
Background:
- Mucopolysaccharidosis type VII (MPS VII) is a genetic disorder characterized by beta-glucuronidase deficiency, leading to lysosomal storage and pathology similar to human MPS VII.
- Previous studies demonstrated that syngeneic bone marrow transplantation (BMT) in MPS VII mice improves survival and reduces lysosomal storage in various organs.
Purpose of the Study:
- To quantify hearing loss in MPS VII mice.
- To determine the impact of early syngeneic BMT on the development of deafness and associated auditory pathology in MPS VII mice.
Main Methods:
- Auditory-evoked brainstem responses (ABR) were used to assess hearing function.
- Histopathological analysis of temporal bone, middle ear, and cochlea was performed.
- BMT was administered at birth to newborn MPS VII mice.
Main Results:
- Eleven weeks post-BMT, MPS VII mice exhibited normal ABR thresholds, contrasting with untreated MPS VII mice showing significantly elevated thresholds (43 dB higher than normal).
- Histological examination revealed the presence of beta-glucuronidase-positive cells in treated mice and reduced pathological changes in the temporal bone and middle ear structures.
- While hearing thresholds increased by 33 weeks, four of six treated mice maintained thresholds 12-32 dB lower than untreated controls.
Conclusions:
- Early syngeneic BMT effectively prevents the onset of hearing loss in MPS VII mice.
- The treatment offers potential for long-term improvement in auditory function, suggesting BMT as a therapeutic strategy for hearing impairment in MPS VII.