Obesity/diabetes in mice with mutations in leptin or leptin receptor genes

Streamson C. Chua, Jr., Lieselotte Herberg, Edward H. Leiter

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Scopus citations


This chapter represents an updating of a previously published review (Herberg and Leiter 2001) of two of the most intensively studied monogenic obesity mutations in the mouse, obese (ob) and diabetes (db). The previous observations that both mutations, although mapping to separate chromosomes, produced nearly identical obesity/diabetes syndromes when studied on a common inbred background, coupled with the results of parabiosis studies (Coleman 1973, 1978) suggested that the two mutations affected a common pathway. This has been confirmed by recent discoveries showing the ob mutation to be a defect in the gene encoding leptin (Lep) and the db mutation to be a defect in the leptin receptor gene (Lepr). This understanding has revolutionized our understanding of how the periphery, particularly fat cells, coordinates management of energy homeostasis with the brain (reviewed in Ahima and Flier 2000). Several other reviews contrast these two mutations with other monogenic obesity-producing genes in the mouse (Kim et al. 1998; McIntosh and Pederson 1999). In the rat, the fatty (fa) mutation on chromosome 5 (and its allele, corpulent, cp) are orthologs of the mouse db mutation. This chapter will help to integrate the extensive early literature describing the physiologic, biochemical, and behavioral effects of the mouse mutations with the more current information gained from the molecular information and the availability of recombinant leptin protein.

Original languageEnglish (US)
Title of host publicationAnimal Models of Diabetes, Second Edition
Subtitle of host publicationFrontiers in Research
PublisherCRC Press
Number of pages42
ISBN (Electronic)9781420009453
ISBN (Print)0849395348, 9780849395345
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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