Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family

Cell. 1996 Apr 19;85(2):281-90. doi: 10.1016/s0092-8674(00)81104-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing / genetics
  • Alternative Splicing / physiology
  • Animals
  • Base Sequence
  • Brain Chemistry / physiology
  • Chromosome Mapping
  • Cloning, Molecular
  • Exons / genetics
  • Gene Expression / physiology
  • Genetic Variation
  • In Situ Hybridization
  • Insulin Resistance / genetics
  • Mice
  • Mice, Obese
  • Molecular Sequence Data
  • Mutation / genetics
  • Obesity / genetics*
  • Polymerase Chain Reaction / methods
  • Proteins / chemistry*
  • Proteins / genetics*
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid


  • Adaptor Proteins, Signal Transducing
  • Proteins
  • RNA, Messenger
  • Tub protein, mouse

Associated data

  • GENBANK/U54643
  • GENBANK/U54644