Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase

Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expres...

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Published in:International journal of molecular medicine 2012-08, Vol.30 (2), p.321-329
Main Authors: JEONG, YEON WOO, LEE, GEUN-SHIK, KIM, JOUNG JOO, PARK, SUN WOO, KO, KYEONG HEE, KANG, MINA, KIM, YU KYUNG, JUNG, EUI-MAN, HYUN, SANG HWAN, SHIN, TAEYOUNG, JEUNG, EUI-BAE, HWANG, WOO SUK
Format: Article
Language:English
Subjects:
canine disease model
Cloning
Deoxyribonucleic acid
Diabetes
DNA
Dogs
Enzymes
Fetuses
Fibroblasts
Genes
Genetic disorders
Genetic engineering
Laboratory animals
Metabolism
phosphoenolpyruvate carboxykinase
somatic cell nuclear transfer
Studies
Transgenic animals
transgenic dogs
type 2 diabetes mellitus
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Summary:Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expressing the phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning efficiency associated with adult or fetal (cloned or natural mating) fibroblasts as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy and cloning rates. The fusion rates were significantly high for fibroblasts from cloned fetuses, but the pregnancy and cloning rates were relatively high for cells from normal fetuses. Based on these data, fetal fibroblasts were selected as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK gene and dual selection marker genes controlled by the PEPCK promoter. The transgenic cells were introduced into oocytes and transferred into five recipient dogs, resulting in two pregnancies. Finally, three puppies were born and confirmed by microsatellite analysis to be genetically identical to the donor. One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This canine disease model may be useful for studying the pathogenesis and/or therapeutic targets of type 2 diabetes mellitus.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2012.993