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A new common integration region (int-3) for mouse mammary tumor virus on mouse chromosome 17
Abstract:
Mus musculus subsp. musculus (Czech II) mammary tumor DNA frequently contains an integrated proviral genome of the mouse mammary tumor virus (MMTV) within a specific 0.5-kilobase-pair region of the cellular genome (designated int-3). Viral integration at this site results in activation of expression of an adjacent cellular gene. We mapped int-3 to mouse chromosome 17 by analysis of PstI-restricted cellular DNAs from mouse-hamster somatic cell hybrids. Restriction analysis of cellular DNA from (C3H/OuJ X Czech II) X Czech II backcross mice established the gene order T-H-2-int-3. These results demonstrated that the int-3 locus is distinct from two other common integration regions for mouse mammary tumor virus (designated int-1 and int-2) in mammary tumor DNA and suggest that several cellular genes may be at risk for virally induced activation during mammary tumor development.
Insights
Mouse mammary tumor virus (MMTV) DNA integration into the int-3 locus on mouse chromosome 17 activates cellular genes, contributing to mammary tumor development. This integration site is distinct from int-1 and int-2.
Area of Science:
- Genetics
- Virology
- Oncology
Background:
- Mouse mammary tumor virus (MMTV) frequently integrates into host DNA during mammary tumor development.
- Specific integration sites can lead to the activation of cellular genes, driving oncogenesis.
Purpose of the Study:
- To map the int-3 integration locus in Mus musculus mammary tumor DNA.
- To determine the chromosomal location of int-3 and its relationship to other MMTV integration sites.
Main Methods:
- Analysis of PstI-restricted cellular DNAs from mouse-hamster somatic cell hybrids.
- Restriction analysis of cellular DNA from backcross mice.
Main Results:
- The int-3 locus was mapped to mouse chromosome 17.
- The gene order T-H-2-int-3 was established.
- The int-3 locus was confirmed to be distinct from int-1 and int-2 integration sites.
Conclusions:
- Viral integration at the int-3 locus activates adjacent cellular genes.
- Multiple cellular genes are susceptible to virally induced activation during mammary tumorigenesis.