title: Study on AAV-mediated gene therapy for diabetes in humanized liver mouse to predict efficacy in humans.
abstract: Most in vivo studies on the conversion to insulin-producing cells with AAV carrying PDX1 gene are performed in rodents. However, there is little information regarding Adeno-associated virus (AAV) carrying PDX1 gene transduced to human liver in vivo because accidental death caused by unpredicted factors cannot be denied, such as the hypoglycemic agent troglitazone with hepatic failure. Here we aim to confirm insulin secretion from human liver transduced with AAV carrying PDX1 gene in vivo and any secondary effect using a humanized liver mouse. As the results, AAV2-PG succeeded to improve the hyperglycemia of STZ-induced diabetic humanized liver mice. Then, the analysis of humanized liver mice revealed that the AAV2-PG was more transducible to humanized liver area than to mouse liver area. In conclusion, the humanized liver mouse model could be used to examine AAV transduction of human hepatocytes in vivo and better predict clinical transduction efficiency than nonhumanized mice.
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan. Electronic address: hashimot@ciea.or.jp.
authors.forename: Haruo
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ogura
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kagawa
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Tomiyama
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Ri-Ichi
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Yagoto
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chijiwa
authors.affiliation: Department of Pathology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000628:therapy; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D049452:Green Fluorescent Proteins
keywords: Adeno-associated virus; Diabetes; Humanized liver mouse; PDX1