A canine model of Alzheimer's disease generated by overexpressing a mutated human amyloid precursor protein

通过过度表达突变的人类淀粉样蛋白前体产生的阿尔茨海默病犬模型

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作者:Geun-Shik Lee, Yeon Woo Jeong, Joung Joo Kim, Sun Woo Park, Kyeong Hee Ko, Mina Kang, Yu Kyung Kim, Eui-Man Jung, Changjong Moon, Sang Hwan Hyun, Kyu-Chan Hwang, Nam-Hyung Kim, Taeyoung Shin, Eui-Bae Jeung, Woo Suk Hwang

Abstract

Canines are considered the most authentic model for studying multifactorial human diseases, as these animals typically share a common environment with man. Somatic cell nuclear transfer (SCNT) technology along with genetic engineering of nuclear donor cells provides a unique opportunity for examining human diseases using transgenic canines. In the present study, we generated transgenic canines that overexpressed the human amyloid precursor protein (APP) gene containing well-characterized familial Alzheimer's disease (AD) mutations. We successfully obtained five out of six live puppies by SCNT. This was confirmed by observing the expression of green fluorescence protein in the body as a visual transgenic marker and the overexpression of the mutated APP gene in the brain. The transgenic canines developed AD-like symptoms, such as enlarged ventricles, an atrophied hippocampus, and β-amyloid plaques in the brain. Thus, the transgenic canines we created can serve as a novel animal model for studying human AD.

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