title: Creation and preliminary characterization of a leptin knockout rat.
abstract: Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various pathways centered on food intake and energy expenditure, including insulin sensitivity, fertility, immune system, and bone metabolism. Here, using zinc finger nuclease technology, we created the first leptin knockout rat. Homozygous leptin null rats are obese with significantly higher serum cholesterol, triglyceride, and insulin levels than wild-type controls. Neither gender produced offspring despite of repeated attempts. The leptin knockout rats also have depressed immune system. In addition, examination by microcomputed tomography of the femurs of the leptin null rats shows a significant increase in both trabecular bone mineral density and bone volume of the femur compared with wild-type littermates. Our model should be useful for many different fields of studies, such as obesity, diabetes, and bone metabolism-related illnesses.
authors.affiliation: Sigma Advanced Genetic Engineering Labs, Sigma-Aldrich Corp., St. Louis, Missouri 63146, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Vaira
authors.forename: Chang
authors.initials: C
authors.lastname: Yang
authors.forename: Aaron
authors.initials: A
authors.lastname: McCoy
authors.forename: Kelly
authors.initials: K
authors.lastname: Keys
authors.forename: Shurong
authors.initials: S
authors.lastname: Xue
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinstein
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Cui
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D004435:Eating / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D005269:Femur / Q000378:metabolism; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D055647:Rats, Transgenic; D014280:Triglycerides / Q000097:blood; D016335:Zinc Fingers
chemical_list: D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol