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

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

doi:10.3892/ijmm.2012.993

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

Authors:
- Yeon Woo Jeong
- Geun-Shik Lee
- Joung Joo Kim
- Sun Woo Park
- Kyeong Hee Ko
- Mina Kang
- Yu Kyung Kim
- Eui-Man Jung
- Sang Hwan Hyun
- Taeyoung Shin
- Eui-Bae Jeung
- Woo Suk Hwang
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Affiliations: SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea, Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kangwon National University, Chucheon 200-701, Republic of Korea, Laboratory of Veterinary Biochemistry and Molecular Biology College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea, Laboratory of Veterinary Embryology and Biotechnology, College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea
Published online on: May 9, 2012 https://doi.org/10.3892/ijmm.2012.993
Pages: 321-329

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Abstract

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.

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