title: Preliminary Characterization of a Leptin Receptor Knockout Rat Created by CRISPR/Cas9 System.
abstract: Leptin receptor, which is encoded by the diabetes (db) gene and is highly expressed in the choroid plexus, regulatesenergy homeostasis, the balance between food intake and energy expenditure, fertility and bone mass. Here, using CRISPR/Cas9 technology, we created the leptin receptor knockout rat. Homozygous leptin receptor null rats are characterized by obesity, hyperphagia, hyperglycemia, glucose intolerance, hyperinsulinemia and dyslipidemia. Due to long-term poor glycemic control, the leptin receptor knockout rats also develop some diabetic complications such as pancreatic, hepatic and renal lesions. In addition, the leptin receptor knockout rats show a significant decrease in bone volume and bone mineral density of the femur compared with their wild-type littermates. Our model has rescued some deficiency of the existing rodent models, such as the transient hyperglycemia of db/db mice in the C57BL/6J genetic background and the delayed onset of glucose intolerance in the Zucker rats, and it is proven to be a useful animal model for biomedical and pharmacological research on obesity and diabetes.
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Bao
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Yuanwu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Guan
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Key Laboratory of Human Disease Animal Model, State Administration of Traditional Chinese Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D015519:Bone Density / Q000235:genetics; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics; D005269:Femur / Q000378:metabolism; D055786:Gene Knockout Techniques / Q000379:methods; D018149:Glucose Intolerance / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006943:Hyperglycemia / Q000235:genetics; D006963:Hyperphagia / Q000235:genetics; D020738:Leptin / Q000235:genetics; D023421:Models, Animal; D009765:Obesity / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D020738:Leptin; D054411:Receptors, Leptin