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Structural analysis of the ras transgene in MMTV/v-Ha-ras transgenic mice
1Department of Veterinary Pathobiology, College of Veterinary Medicine, Ohio State University, Columbus 43210.
Abstract:
Transgenic animals are becoming increasingly important in laboratory animal research. In cancer research, the role of specific genes in tumorigenesis can be directly tested in live animals by using transgenic animal technology. Since DNA-damaging carcinogens are not required to initiate tumors in transgenic animals, these models are particularly useful in the analysis of genetic alterations associated with tumorigenesis. Southern blot analysis was used to assess the copy number, structure, and methylation status of the ras trans-gene in MMTV/v-Ha-ras transgenic mice. The results indicate that MMTV/v-Ha-ras transgenic mice carry about 20 copies of the ras transgene. The integrated ras transgene is maintained without major rearrangements in normal tissues and in mammary tumors. The ras transgene is methylated in liver, hypomethylated at a single site in normal mammary tissue, and hypomethylated at two sites in mammary tumors. Transgenic animals provide a new model to assess genetic alteration in tumorigenesis.
Insights
Transgenic mice models offer a novel way to study cancer development by analyzing genetic alterations. Researchers found the ras transgene in these mice remained stable, with methylation patterns changing during tumor formation.
Area of Science:
- Laboratory animal research
- Cancer research
- Transgenic animal technology
Background:
- Transgenic animals are crucial for studying gene function in vivo.
- They enable direct testing of specific genes in tumorigenesis without carcinogens.
- This facilitates the analysis of genetic alterations linked to cancer development.
Purpose of the Study:
- To assess the copy number, structure, and methylation status of the ras transgene in MMTV/v-Ha-ras transgenic mice.
- To characterize the genetic behavior of the transgene in normal and tumor tissues.
Main Methods:
- Southern blot analysis was employed.
- The analysis focused on the ras transgene within MMTV/v-Ha-ras transgenic mice.
Main Results:
- MMTV/v-Ha-ras transgenic mice possess approximately 20 copies of the ras transgene.
- The transgene was structurally maintained without significant rearrangements in normal tissues and mammary tumors.
- Differential methylation patterns of the ras transgene were observed: methylated in liver, hypomethylated in normal mammary tissue, and further hypomethylated in mammary tumors.
Conclusions:
- Transgenic animals, specifically MMTV/v-Ha-ras mice, serve as a valuable model for investigating genetic alterations in tumorigenesis.
- The stability of the transgene and its altered methylation status in tumors provide insights into cancer development mechanisms.