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Vacuolar degeneration of skeletal muscle in transgenic mice overexpressing ORP150
Tomohiro Kobayashi1, Yuko Takita, Atsuko Suzuki
1HSP Research Institute, Kyoto Research Park, Kyoto, Japan.
Abstract:
ORP150 is a hypoxic stress-induced protein located in the endoplasmic reticulum. Transgenic mice overexpressing ORP150 (ORP-Tg) exhibit vacuolar degeneration in the heart. To determine whether vacuolization is present in skeletal muscle, we pathologically examined ORP-Tg mice. After 60 days of age, severe vacuolization was found in the soleus muscles of the hind legs of the ORP-Tg mice. Immunohistochemical staining of ORP150 revealed co-localization of ORP150 and vacuolization in the affected cells. Electron microscopy revealed a marked increase in the number of rough-surfaced endoplasmic reticula (rER) and distention of the cisterna. These findings suggest that overexpression of ORP150 causes accumulation of ORP150 in the rER, resulting in vacuolar degeneration in the skeletal muscle of ORP-Tg mice.
Insights
Overexpression of ORP150 in transgenic mice causes vacuolar degeneration in skeletal muscle. This vacuolization is linked to endoplasmic reticulum stress and accumulation of ORP150 in muscle cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Pathology
Background:
- ORP150 is a protein induced by hypoxic stress and localized to the endoplasmic reticulum.
- Transgenic mice overexpressing ORP150 (ORP-Tg) show vacuolar degeneration in cardiac muscle.
Purpose of the Study:
- To investigate the presence and characteristics of vacuolization in the skeletal muscle of ORP-Tg mice.
- To determine the role of ORP150 in skeletal muscle pathology.
Main Methods:
- Pathological examination of soleus muscles from ORP-Tg mice.
- Immunohistochemical staining for ORP150.
- Electron microscopy of affected skeletal muscle tissue.
Main Results:
- Severe vacuolization was observed in the soleus muscles of ORP-Tg mice by 60 days of age.
- ORP150 co-localized with vacuolization in affected skeletal muscle cells.
- Electron microscopy revealed increased rough endoplasmic reticulum (rER) and cisternal distention.
Conclusions:
- Overexpression of ORP150 leads to its accumulation in the rER of skeletal muscle cells.
- This accumulation results in vacuolar degeneration in the skeletal muscle of ORP-Tg mice.
- ORP150 plays a role in skeletal muscle pathology under conditions of overexpression.
