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Hereditary suppression of lethal (2) giant larvae malignant tumor development in Drosophila by gene transfer
M Opper1, G Schuler, B M Mechler
1Institute of Genetics, Johannes Gutenberg University, Mainz, GFR.
Abstract:
Homozygous mutations of the recessive oncogene lethal-(2) giant larvae (l(2)gl) of Drosophila melanogaster cause lethal neoplasms of the imaginal discs and the brain hemisphere. A 13-kb DNA segment spanning the l(2)gl+ locus has been inserted into P element vectors and used for P-mediated transformation. The P-l(2)gl+ transposons have been introduced into the germ line of heterozygous l(2)gl-/+ flies and were shown by backcrossing to fully rescue the homozygous l(2)gl deficient animals, which otherwise would have died of brain and imaginal disc neoplasms. Further genetic backcrossing with l(2)gl deficiencies characterized by deletions of increased sizes involving the left end of chromosome 2 indicated that a relatively large region of developmentally regulated DNA sequence adjacent to the l(2)gl gene is apparently not essential for the viability and fertility of the fly. These experiments indicate that all the genetic information specified by the l(2)gl+ gene is contained within this 13-kb DNA segment and demonstrates that the development of neuroblastomas and imaginal disc tumors results from the absence of l(2)gl function. When this function is restored, tumor development is completely suppressed.
Insights
Mutations in the lethal-(2) giant larvae (l(2)gl) gene cause fatal tumors in Drosophila. Restoring l(2)gl function using a 13-kb DNA segment completely suppressed tumor development, proving its essential role.
Area of Science:
- Developmental biology
- Cancer genetics
- Drosophila melanogaster research
Background:
- Recessive oncogenes, such as lethal-(2) giant larvae (l(2)gl), are crucial for preventing uncontrolled cell proliferation.
- Mutations in l(2)gl lead to lethal neoplasms in imaginal discs and brain hemispheres in Drosophila melanogaster.
Purpose of the Study:
- To identify and characterize the DNA segment responsible for the l(2)gl+ gene function.
- To demonstrate the role of l(2)gl in suppressing tumor development in Drosophila.
Main Methods:
- Isolation and cloning of a 13-kb DNA segment containing the l(2)gl+ locus.
- P-mediated transformation to introduce the P-l(2)gl+ transposons into Drosophila germ lines.
- Genetic backcrossing to assess the rescue of homozygous l(2)gl-deficient flies and tumor suppression.
Main Results:
- A 13-kb DNA segment was identified that fully rescues homozygous l(2)gl-deficient flies, preventing lethal neoplasms.
- The rescued flies were viable and fertile, indicating the sufficiency of the 13-kb segment for l(2)gl function.
- Adjacent DNA sequences were found to be non-essential for viability and fertility.
Conclusions:
- The 13-kb DNA segment contains all essential genetic information for the l(2)gl+ gene.
- The absence of l(2)gl function directly causes neuroblastomas and imaginal disc tumors.
- Restoration of l(2)gl function completely suppresses tumor formation, highlighting its critical role in preventing cancer.