A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat

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 estab...

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Main Authors: Norihide Yokoi, Masayuki Hoshino, Shihomi Hidaka, Eri Yoshida, Masayuki Beppu, Ritsuko Hoshikawa, Katsuko Sudo, Akihiko Kawada, Sadaaki Takagi, Susumu Seino
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2013/103731
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author Norihide Yokoi
Masayuki Hoshino
Shihomi Hidaka
Eri Yoshida
Masayuki Beppu
Ritsuko Hoshikawa
Katsuko Sudo
Akihiko Kawada
Sadaaki Takagi
Susumu Seino
author_facet Norihide Yokoi
Masayuki Hoshino
Shihomi Hidaka
Eri Yoshida
Masayuki Beppu
Ritsuko Hoshikawa
Katsuko Sudo
Akihiko Kawada
Sadaaki Takagi
Susumu Seino
author_sort Norihide Yokoi
collection DOAJ
description 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-Leprfa (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.
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institution Kabale University
issn 2314-6745
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publishDate 2013-01-01
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series Journal of Diabetes Research
spelling doaj-art-3bd25748bcaf4c7996402c3c827dc2f52025-08-20T03:55:41ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/103731103731A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM RatNorihide Yokoi0Masayuki Hoshino1Shihomi Hidaka2Eri Yoshida3Masayuki Beppu4Ritsuko Hoshikawa5Katsuko Sudo6Akihiko Kawada7Sadaaki Takagi8Susumu Seino9Division 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, JapanHoshino Laboratory Animals, Inc., Ibaraki 306-0606, JapanDivision 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, JapanDivision 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, JapanDivision 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, JapanDivision 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, JapanAnimal Research Center, Tokyo Medical University, Tokyo 160-8402, JapanJapan SLC, Inc., Hamamatsu 431-1103, JapanJapan SLC, Inc., Hamamatsu 431-1103, JapanDivision 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, JapanThe 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-Leprfa (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.http://dx.doi.org/10.1155/2013/103731
spellingShingle Norihide Yokoi
Masayuki Hoshino
Shihomi Hidaka
Eri Yoshida
Masayuki Beppu
Ritsuko Hoshikawa
Katsuko Sudo
Akihiko Kawada
Sadaaki Takagi
Susumu Seino
A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
Journal of Diabetes Research
title A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
title_full A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
title_fullStr A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
title_full_unstemmed A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
title_short A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat
title_sort novel rat model of type 2 diabetes the zucker fatty diabetes mellitus zfdm rat
url http://dx.doi.org/10.1155/2013/103731
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