title: Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.
abstract: The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Kleyn
authors.forename: W
authors.initials: W
authors.lastname: Fan
authors.forename: S G
authors.initials: SG
authors.lastname: Kovats
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: J C
authors.initials: JC
authors.lastname: Pulido
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: L R
authors.initials: LR
authors.lastname: Berkemeier
authors.forename: D J
authors.initials: DJ
authors.lastname: Misumi
authors.forename: L
authors.initials: L
authors.lastname: Holmgren
authors.forename: O
authors.initials: O
authors.lastname: Charlat
authors.forename: E A
authors.initials: EA
authors.lastname: Woolf
authors.forename: O
authors.initials: O
authors.lastname: Tayber
authors.forename: T
authors.initials: T
authors.lastname: Brody
authors.forename: P
authors.initials: P
authors.lastname: Shu
authors.forename: F
authors.initials: F
authors.lastname: Hawkins
authors.forename: B
authors.initials: B
authors.lastname: Kennedy
authors.forename: L
authors.initials: L
authors.lastname: Baldini
authors.forename: C
authors.initials: C
authors.lastname: Ebeling
authors.forename: G D
authors.initials: GD
authors.lastname: Alperin
authors.forename: J
authors.initials: J
authors.lastname: Deeds
authors.forename: N D
authors.initials: ND
authors.lastname: Lakey
authors.forename: J
authors.initials: J
authors.lastname: Culpepper
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: M A
authors.initials: MA
authors.lastname: Glücksmann-Kuis
authors.forename: G A
authors.initials: GA
authors.lastname: Carlson
authors.forename: G M
authors.initials: GM
authors.lastname: Duyk
authors.forename: K J
authors.initials: KJ
authors.lastname: Moore
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000502:physiology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D014644:Genetic Variation; D017403:In Situ Hybridization; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D012333:RNA, Messenger; C098988:Tub protein, mouse