y genes; genetic and physical maps were obtained, the gene was then isolated and the mutation detected. In mice, five single-gene mutations resulting in an obese phenotype have been described. The obese mutation (ob) was the first of the recessive obesity mutations. Previous experiments with mutant and wild-type mice have shown ob mice to be deficient regarding a blood-borne factor that regulates nutrient intake and metabolism (8).
The authors report cloning and sequencing of the mouse ob gene and its human homologue. "ob encodes a 4.5-kilobase (kb) adipose tissue messenger RNA with a highly conserved 167-animo-acid open reading frame." The amino-acid sequence predicted is 84 percent identical between human and mouse, with features of a secreted protein (8:425). Molecular and classical genetic markers show the mouse ob and db genes mapped to proximal chromosome 6 and midchromosome 4, respectively. If there are human homologs of ob and db, they are suggested to map to human chromosomes 7q and 1p, respectively. Molecular techniques allowing the cloning of single-gene mutations and the dissection of polygenic traits are thought to be applicable to genetic studies of obese mammals. Previous experiments which involved the cloning of mammalian disease genes and the mapping of genetic loci conferring Type I diabetes susceptibility and hypertension in mice and rats, shows this capability. Obesity gene cloning may possibly provide insight into molecular mechanisms controlling body composition by effects on food intake and energy expenditure (3).
It is suggested that "the ob gene product may function as part of a signalling pathway from adipose tissue that acts to reg
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