The Genetics of Obesity, Part II

Rodents Lead the Way

The study of obesity genetics dates back more than half a century. In 1949, researchers at the Jackson Laboratories identified a remarkably fat mouse, which they determined carried a spontaneous mutation in an unidentified gene. They named this the "obese" (ob/ob) mouse. Over the next few decades, researchers identified several other genetically obese mice with spontaneous mutations, including diabetic (db/db) mice, "agouti" (Avy) mice, and "Zucker" (fa/fa) rats.

At the time of discovery, no one knew where the mutations resided in the genome. All they knew is that the mutations were in single genes, and they resulted in extreme obesity. Researchers recognized this as a huge opportunity to learn something important about the regulation of body fatness in an unbiased way. Unbiased because these mutations could be identified with no prior knowledge about their function, therefore the investigators' pre-existing beliefs about the mechanisms of body fat regulation could have no impact on what they learned. Many different research groups tried to pin down the underlying source of dysfunction: some thought it was elevated insulin and changes in adipose tissue metabolism, others thought it was elevated cortisol, and a variety of other hypotheses.

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