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Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene
Takayuki Tsuchiya1, Kiyoshi Kobayashi, Tetsuya Sakairi
1Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc, Chiba-ken, Japan. Tsuchiya.Takayuki@mf.m-pharma.co.jp
Abstract:
Skeletal myopathy was found in almost all-transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle fiber size, centrally placed nuclei, regenerating fibers, and interstitial fibrosis were evident; hyalinization and necrosis were sometimes observed in the skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory changes in the skeletal muscle or abnormality of adjacent peripheral nerve were not observed. The features were essentially similar to those of muscular dystrophy. Although the severity was relatively mild compared to 34-week-old rasH2 mice, the skeletal myopathy was also observed in younger male (10 weeks of age) rasH2 mice. In nontransgenic littermates, skeletal myopathy was not observed. The mRNA of human c-Ha-ras product was detected in femoral muscle from the rasH2 mice by RT-PCR. In conclusion, these data suggest that skeletal myopathy is occurring in almost all rasH2 mice. Integration of c-Ha-ras gene is thought to be crucial to pathogenesis of skeletal myopathy in the rasH2 mice. Further characterization of the muscular lesion and its pathogenesis are needed to explore the possibility of rasH2 mouse becoming a new model for muscular dystrophy.
Insights
Transgenic rasH2 mice exhibit skeletal myopathy, characterized by muscle fiber abnormalities and fibrosis, suggesting the integrated human c-Ha-ras gene is key to its development. These findings indicate the rasH2 mouse may serve as a novel model for muscular dystrophy research.
Area of Science:
- Genetics
- Pathology
- Animal Models
Background:
- Transgenic mouse models are crucial for studying genetic diseases.
- Skeletal muscle disorders present significant research challenges.
- The c-Ha-ras gene's role in myopathy requires further investigation.
Purpose of the Study:
- To investigate skeletal myopathy in transgenic rasH2 mice.
- To determine if the integrated human c-Ha-ras gene causes muscle pathology.
- To evaluate the rasH2 mouse as a potential model for muscular dystrophy.
Main Methods:
- Histopathological examination of skeletal muscles (femoralis, pectoralis) in rasH2 and wild-type mice.
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect human c-Ha-ras mRNA in muscle tissue.
- Comparative analysis of muscle morphology across different age groups of rasH2 mice.
Main Results:
- Almost all rasH2 mice displayed skeletal myopathy, unlike non-transgenic littermates.
- Microscopic findings included muscle fiber size variation, central nuclei, regeneration, fibrosis, and occasional hyalinization/necrosis.
- Human c-Ha-ras mRNA was detected in the femoral muscle of rasH2 mice.
- Skeletal myopathy was observed in both younger (10 weeks) and older (34 weeks) male rasH2 mice.
Conclusions:
- Skeletal myopathy is a consistent finding in rasH2 mice.
- The integration of the human c-Ha-ras gene is implicated in the pathogenesis of this myopathy.
- The rasH2 mouse model warrants further study for its potential in muscular dystrophy research.