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Published on: June 15, 2017
Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice
1Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
Summary
Researchers manipulated gene copies in mice to study quantitative traits like hypertension. Increasing angiotensinogen gene copies altered protein levels, showing a promising method for genetic research.
Area of Science:
- Genetics
- Molecular Biology
- Quantitative Trait Analysis
Background:
- Studying complex genetic traits requires methods to alter gene expression without changing DNA sequence or location.
- Essential hypertension is a complex quantitative trait that would benefit from such experimental approaches.
Purpose of the Study:
- To develop and validate a method for manipulating gene expression by altering gene copy number in mice.
- To investigate the effect of varying angiotensinogen gene copy numbers on its expression levels.
Main Methods:
- Utilized targeted gene disruption and duplication (gap-repair gene targeting) in genetically identical mice.
- Generated mice with one, two, or three functional copies of the angiotensinogen gene.
- Analyzed steady-state plasma angiotensinogen levels in mice with different gene copy numbers.
Main Results:
- Mice with one copy of the angiotensinogen gene showed ~35% of normal plasma levels.
- Mice with three copies of the angiotensinogen gene showed ~124% of normal plasma levels.
- Demonstrated a progressive and significant correlation between angiotensinogen gene copy number and protein levels.
Conclusions:
- Altering gene copy number via gene targeting is a viable and promising approach for quantitative genetics research.
- This method facilitates the study of gene function and quantitative traits without needing detailed knowledge of regulatory sequences.
- The technique allows for precise manipulation of gene dosage for experimental analysis.
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