A canine model of Alzheimer's disease generated by overexpressing a mutated human amyloid precursor protein.
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.
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chucheon, Gangwon 200‑701, Republic of Korea.
Geun-Shik
GS
Lee
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Yeon Woo
YW
Jeong
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Joung Joo
JJ
Kim
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Sun Woo
SW
Park
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Kyeong Hee
KH
Ko
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Mina
M
Kang
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Yu Kyung
YK
Kim
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Eui-Man
EM
Jung
Department of Veterinary Anatomy, College of Veterinary Medical Institute, Chonnam National University, Gwangju, Gyeonggi 500-757, Republic of Korea.
Changjong
C
Moon
Laboratory of Veterinary Embryology and Biotechnology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Sang Hwan
SH
Hyun
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Kyu-Chan
KC
Hwang
Department of Animal Science, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Nam-Hyung
NH
Kim
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Taeyoung
T
Shin
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Eui-Bae
EB
Jeung
SooAm Biotech Research Foundation, Seoul 152-904, Republic of Korea.
Woo Suk
WS
Hwang
D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005347:Fibroblasts / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D050505:Mutant Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D018800:Thy-1 Antigens / Q000235:genetics; D019076:Transgenes / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D050505:Mutant Proteins; D018800:Thy-1 Antigens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins