title: A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat.
abstract: The Zucker fatty (ZF) rat harboring a missense mutation (fatty, fa) in the leptin receptor gene (Lepr) develops obesity without diabetes; Zucker diabetic fatty (ZDF) rats derived from the ZF strain exhibit obesity with diabetes and are widely used for research on type 2 diabetes (T2D). Here we establish a novel diabetic strain derived from normoglycemic ZF rats. In our ZF rat colony, we incidentally found fa/fa homozygous male rats having reproductive ability, which is generally absent in these animals. During maintenance of this strain by mating fa/fa males and fa/+ heterozygous females, we further identified fa/fa male rats exhibiting diabetes. We then performed selective breeding using the fa/fa male rats that exhibited relatively high blood glucose levels at 10 weeks of age, resulting in establishment of a diabetic strain that we designated Hos:ZFDM-Lepr(fa) (ZFDM). These fa/fa male rats developed diabetes as early as 10 weeks of age, reaching 100% incidence by 21 weeks of age, while none of the fa/+ male rats developed diabetes. The phenotypic characteristics of this diabetic strain are distinct from those of normoglycemic ZF rats. ZFDM rat strain having high reproductive efficiency should serve as a more useful animal model of T2D.
authors.affiliation: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan ; Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Yokoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hoshino
authors.forename: Shihomi
authors.initials: S
authors.lastname: Hidaka
authors.forename: Eri
authors.initials: E
authors.lastname: Yoshida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Beppu
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Hoshikawa
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawada
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Takagi
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino