Phenotype-linked amino acid alteration in leptin receptor cDNA from Zucker fatty (fa/fa) rat

The mouse obese (ob) gene product (leptin), expressed specifically in adipose cells, regulates energy balance in mice. Both mouse diabetes (db) and rat fatty (fa) gene products are thought to play major roles in leptin signaling pathways in the hypothalamic area. Mutations of these gents in murines result in marked obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. Reported herein are thr cloning and sequencing of one of spliced valiant forms of rat leptin receptor (OB-R) cDNA with a short intracellular domain. In the Zucker (fa/fa) rat, no changes in either the gene structure or the expression levels were observed. However, phenotype-linked nucleotide alteration exists in the cDNA from Zucker (fa/fa) rat, which results in an amino acid substitution. (C) 1996 Academic Press, Inc.