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Transgenic mouse models for tumor suppressor genes
G S Palapattu1, S Bao, T R Kumar
1Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
The identification and cloning of tumor suppressor genes has mostly relied on familial human cancer predisposition syndromes and reverse genetics. Recent advances in manipulating the mouse genome by gene targeting techniques in embryonic stem (ES) cells has led to the generation of mutant mouse models mimicking many human syndromes. Mice lacking one or both alleles of known tumor suppressor genes have been generated to evaluate the normal function of these genes in vivo. These mice have proven to be highly susceptible to tumor development, indicating that the mouse is a potent in vivo assay system for tumor suppressor genes. The initiation of gonadal tumor development in mice lacking both copies of the alpha-inhibin gene demonstrates that this assay is also useful for identifying new tumor suppressor genes. In the future, murine ES cell/gene targeting strategies will continue to be used to identify novel tumor suppressors and analyze their in vivo roles in growth control.
Insights
Mice lacking tumor suppressor genes are susceptible to tumors, proving mice are a potent assay for gene function. The alpha-inhibin gene
Area of Science:
- Cancer biology
- Genetics
- Molecular biology
Background:
- Tumor suppressor genes are typically identified through human cancer syndromes and reverse genetics.
- Gene targeting in mouse embryonic stem (ES) cells enables the creation of mutant mouse models that mimic human genetic disorders.
Purpose of the Study:
- To evaluate the in vivo function of tumor suppressor genes.
- To establish the mouse as an in vivo assay system for tumor suppressor genes.
- To explore the utility of this system for identifying novel tumor suppressor genes.
Main Methods:
- Generation of mutant mouse models using gene targeting in ES cells.
- Analysis of tumor development in mice lacking specific tumor suppressor gene alleles.
- Focus on gonadal tumor development in mice lacking alpha-inhibin gene copies.
Main Results:
- Mice lacking tumor suppressor gene alleles exhibit high susceptibility to tumor development.
- The absence of both alpha-inhibin gene copies in mice initiates gonadal tumor development.
- This demonstrates the mouse's efficacy as an in vivo assay for tumor suppressor genes.
Conclusions:
- The mouse serves as a powerful in vivo system for studying tumor suppressor genes.
- The alpha-inhibin gene's role in tumor suppression is confirmed through mouse models.
- Future research will leverage murine ES cell/gene targeting for novel tumor suppressor discovery and functional analysis.