Coleman hypothesized that the product of the ob+ gene was the appetite-suppressing hormone. Therefore, the homozygous ob/ob mutant would be unable to synthesize that hormone, and its circulating level would be zero. Coleman also hypothesized that the product of the db+ gene was the the receptor for the appetite-suppressing hormone. Therefore, the homozygous db?db mutant would be able to respond to it. It would eat excessively and produce large amounts of body fat, which in turn would produce large amounts of appetite-suppressing hormone. In the absence of a receptor, the db/db mutant's hormone level would remain abnormally high.
Both the ob/ob mutant and the db/db mutant are obese because neither is capable of suppressing its appetite. The ob/ob mutant produces no appetite suppressing hormone and so eats excessively. The db/db mutant cannot respond to the appetite-suppressing hormone and therefore eats excessively.
