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Establishment of a novel neuroblastoma mouse model
Hiroshi Iwakura1, Hiroyuki Ariyasu, Naotetsu Kanamoto
1Ghrelin Research Project, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan. hiwaku@kuhp.kyoto-u.ac.jp
Abstract:
Neuroblastoma is the most common childhood cancer, which arises from sympathetic neural precursors. Because the prognosis of advanced neuroblastoma is known to be poor, developments of new anti-cancer drugs are desperately needed. For screening of therapeutic drugs for neuroblastoma, genetically engineered animal models would be useful. In an attempt to obtain transgenic mice carrying simian virus 40 T-antigen gene under control of tetracycline responsive elements with cytomegalovirus promoter, we found one line of mice exhibiting bilateral adrenal tumors by leakage expression of T-antigen in adrenal gland. These adrenal tumors contained small round tumor cells with increased N/C ratio, showing chromogranin A and neuron specific enolase-like immunoreactivity. By electron microscopy, tumor cells containing neuritic processes with synaptic vesicles surrounding them were observed. The plasma levels of dopamine were significantly elevated in these transgenic mice. MYCN expression levels were significantly elevated in these tumors. These findings indicated that the adrenal tumor was a neuroblastoma. This mouse model would be a useful tool for development of chemotherapeutic drugs and understanding the etiology of neuroblastoma.
Insights
Researchers developed a new mouse model for neuroblastoma, the most common childhood cancer. This model, featuring adrenal tumors, will aid in discovering new anti-cancer drugs and understanding the disease
Area of Science:
- Developmental biology
- Oncology
- Genetics
Background:
- Neuroblastoma is a prevalent childhood cancer originating from sympathetic neural precursors.
- Advanced neuroblastoma has a poor prognosis, necessitating novel therapeutic strategies.
- Genetically engineered animal models are crucial for screening anti-cancer drugs.
Purpose of the Study:
- To develop a genetically engineered mouse model for neuroblastoma research.
- To investigate the potential of a transgenic mouse line for studying neuroblastoma etiology and treatment.
Main Methods:
- Generation of transgenic mice carrying the simian virus 40 T-antigen gene under a tetracycline-responsive promoter.
- Histopathological and immunohistochemical analysis of adrenal tumors.
- Electron microscopy to examine tumor cell ultrastructure.
- Measurement of plasma dopamine levels and MYCN expression in tumors.
Main Results:
- A transgenic mouse line spontaneously developed bilateral adrenal tumors resembling human neuroblastoma.
- Tumor cells exhibited characteristic neuroblastoma markers (chromogranin A, neuron-specific enolase) and ultrastructural features.
- Elevated plasma dopamine and MYCN expression were observed in the tumor-bearing mice.
Conclusions:
- The developed transgenic mouse line serves as a valuable preclinical model for neuroblastoma.
- This model facilitates the development of novel chemotherapeutic agents.
- It aids in advancing the understanding of neuroblastoma's underlying causes and progression.
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