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Forward Genetic Approach to Uncover Stress Resistance Genes in Mice — A High-throughput Screen in ES Cells
Published on: November 11, 2015
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Functional genomics screening utilizing mutant mouse embryonic stem cells identifies novel radiation-response genes
Kimberly Loesch1, Stacy Galaviz1, Zaher Hamoui2
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.
Plos One
|April 9, 2015
Summary
Identifying genes that affect radiation response is key for cancer therapy. Screening mutant stem cells revealed new genes, like Dstn and Map2k6, that could sensitize cancer cells to radiation.
Area of Science:
- Genetics
- Cancer Biology
- Radiation Oncology
Background:
- Optimizing radiotherapy requires understanding genetic factors influencing patient response.
- Individualizing cancer treatment necessitates identifying genes that confer radiation sensitivity or resistance.
Purpose of the Study:
- To identify novel genes involved in modulating cellular response to radiation.
- To screen a library of mutant murine embryonic stem cells (ESCs) for radiation response phenotypes.
Main Methods:
- Screening over 500 mutant ESC lines for cell viability and gene expression after radiation exposure.
- Utilizing proteomic analysis to identify enriched biological pathways.
- Focusing on a cancer-relevant subset of mutant ESCs.
Main Results:
- Identified 13 genes influencing radiation response, including 6 previously unknown.
- Proteomic analysis revealed enrichment for genes in cellular component disassembly and growth regulation.
- Dstn and Map2k6 were identified as potential sensitizing targets, while Iqgap and Vcan were identified as resistance targets.
Conclusions:
- Screening mutant ESCs is an effective strategy for discovering genes that impact radiation response.
- The identified genes offer potential therapeutic targets for enhancing radiotherapy efficacy.
- This research contributes to the development of personalized cancer treatment strategies.
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