title: Abnormal splicing of the leptin receptor in diabetic mice.
abstract: Mutations in the mouse diabetes (db) gene result in obesity and diabetes in a syndrome resembling morbid human obesity. Previous data suggest that the db gene encodes the receptor for the obese (ob) gene product, leptin. A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db. This receptor maps to the same 300-kilobase interval as db, and has at least six alternatively spliced forms. One of these splice variants is expressed at a high level in the hypothalamus, and is abnormally spliced in C57BL/Ks db/db mice. The mutant protein is missing the cytoplasmic region, and is likely to be defective in signal transduction. This suggests that the weight-reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus.
authors.affiliation: Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Proenca
authors.forename: J M
authors.initials: JM
authors.lastname: Montez
authors.forename: K M
authors.initials: KM
authors.lastname: Carroll
authors.forename: J G
authors.initials: JG
authors.lastname: Darvishzadeh
authors.forename: J I
authors.initials: JI
authors.lastname: Lee
authors.forename: J M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014018:Tissue Distribution
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse