Creation and Preliminary Characterization of a Leptin Knockout Rat

• Published in: Endocrinology (Philadelphia) Vol. 153; no. 11; pp. 5622 - 5628
• Main Authors: Vaira, Sergio, Yang, Chang, McCoy, Aaron, Keys, Kelly, Xue, Shurong, Weinstein, Edward J, Novack, Deborah V, Cui, Xiaoxia
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01-11-2012; Oxford University Press
• Subjects: Adipocytes; Animals; Biological and medical sciences; Body Weight - genetics; Bone Density - genetics; Bone mineral density; Bone turnover; Cancellous bone; Cholesterol; Cholesterol - blood; Computed tomography; Diabetes mellitus; Eating - genetics; Energy expenditure; Energy Metabolism - genetics; Femur; Femur - metabolism; Fertility; Food intake; Fundamental and applied biological sciences. Psychology; Immune system; Insulin; Insulin - blood; Leptin; Leptin - genetics; Leptin - metabolism; Nuclease; Obesity; Obesity - genetics; Obesity - metabolism; Offspring; Phenotype; Rats; Rats, Transgenic; Technical Communication; Triglycerides; Triglycerides - blood; Vertebrates: endocrinology; Zinc finger proteins; Zinc Fingers; Characterization; Vertebrata; Mammalia; Rat; Animal; Leptin; Rodentia; Adipokine; Mutation
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2012-1462

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.