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A molecular genetic method for genotyping fatty (fa/fa) rats
J W Smoller1, G E Truett, J Hirsch
1Laboratory of Human Behavior and Metabolism, Rockefeller University, New York, New York 10021.
The American Journal of Physiology
|January 1, 1993
Summary
Researchers identified the genetic cause of obesity in Zucker fatty rats using DNA analysis. This molecular method accurately detects the obesity gene (fa/fa) in rats from birth, aiding early research into metabolic diseases.
Area of Science:
- Genetics
- Molecular Biology
- Animal Models
Background:
- The genetic basis for Zucker fatty (fa/fa) rat obesity remains elusive after 30 years of research.
- Previous methods for identifying obese rats relied on phenotypic traits observable only after two weeks of age, missing early disease stages.
Purpose of the Study:
- To develop and validate a molecular genetic method for precise genotyping of Zucker fatty rats.
- To enable early detection of the obesity mutation (fa/fa) for studying its earliest phenotypic effects.
Main Methods:
- Utilized restriction fragment length polymorphism (RFLP) with a human DNA probe (VC85) linked to the rat fa locus.
- Genotyped F2 progeny from a Zucker (13M) x Brown Norway (BN) fa/+ F1 intercross.
- Isolated DNA from rat tails (early) or organs (at 5-6 weeks) for RFLP analysis.
Main Results:
- RFLP analysis demonstrated over 99% accuracy in identifying obese (fa/fa) Zucker rats.
- The method allowed for genotyping at any age, including prenatally, and distinguished heterozygous from homozygous littermates.
Conclusions:
- A highly accurate RFLP-based molecular genetic method can identify Zucker fatty rats early in development.
- This technique facilitates the study of gene dosage effects and the earliest phenotypic manifestations of the fa mutation.