Transgenic Brain Tumor Models

Brain tumors are still a serious threat to human health and life. The establishment of experimental animal models of tumors provides a highly simulated tool for studying their pathogenesis, and biological characteristics and testing various therapeutic approaches. Early on, chemical-induced brain tumor models, virus-induced models, and homozygous and xenograft models have been established successively. With the development of modern molecular biology techniques, transgenic animal models will become another key model for studying brain tumors.

Our transgenic animal model building services for brain tumors

Transgenic animals are the product of modern genetic engineering technology, which introduces exogenous genes into the chromosomal genome of the host and passes them stably to the offspring. Since the genotype of the host can be changed, the exogenous gene can be expressed in the animal. Transgenic animals have become a powerful tool for studying the molecular biology of brain tumorigenesis, and Alfa Cytology can provide customers with the preparation of transgenic animal models of brain tumors based on two basic ideas.

• Introduce an oncogenic gene that is expressed in a specific cell that can utilize the promoter of the gene. Although the gene may not be sufficient to transform normal cells into tumor cells, it may have a synergistic effect on other genetic alterations, making it more likely to induce tumorigenesis.
• Gene knockout, which results in the deletion of expression of specific genes that encode proteins that may happen to have a role in suppressing tumorigenesis.

This is because the type of brain tumor produced by genetic animals is determined by abnormalities in specific signaling pathways and the cells in which they occur. Thus, we can induce gliomas by activating certain growth factors that control the signaling pathway of glial cell differentiation, such as medulloblastoma by activating the signaling pathway of cerebellar granule cell precursor differentiation. Even if the same tumor is produced, the degree of malignancy varies depending on the gene under control.

Preparation of transgenic brain tumor animals by transduction of viral oncogenes

The V-src gene initiated by the glial fibrillary acetate protein (GFAP) promoter leads to the development of transgenic murine astrocytomas. We introduced the multiplex tumor virus intermediate T antigen gene into somatic cells of GFAP-positive expressing animals, which induced the generation of mixed gliomas. We were able to generate multiple types of gliomas, including glioblastoma multiforme, by viral transduction of the PDGF gene after integration into a mixture of multiple cells in vivo. We were able to induce glioblastoma multiforme after introducing active Akt and Ras genes into glial precursor cells.

Building transgenic animal models of medulloblastoma and choroid plexus papillomas (CCPs)

• Medulloblastoma originates from the cerebellar neuroectoderm, and the signal transduction process of its cell differentiation is regulated by SHH and its receptor PTCH, which has a strong inhibitory effect on it. Therefore, inactivation or deletion of PTCH expression is oncogenic and can give rise to a variety of tumors, including medulloblastoma.
• CCPs originate from ventricular choroid plexus tissue and their exact differentiation process is not yet understood. CCPs can occur after we express the SV40 large T antigen gene generated by the upstream promoter of polymorphic adenovirus SV40 in choroid plexus cells.

Applications

• Verifying therapeutic efficacy
• Validation of potential oncogenes and drug targets
• Analyzing the impact of the tumor microenvironment
• Evaluate mechanisms of drug resistance

Alfa Cytology offers its customers the service of preparing transgenic animal models of brain tumors that better mimic the histopathological and molecular characteristics of human brain tumors and exhibit better genetic heterogeneity. It can reflect the brain tumor cells themselves and the cellular and other interactions in the tumor microenvironment. Please feel free to contact with your needs to build a more rational and effective transgenic animal model of a brain tumor in conjunction with clinical patient studies.