Bhlhe40, a potential diabetic modifier gene on Dbm1 locus, negatively controls myocyte fatty acid oxidation
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- Takeshita Shigeru
- Department of Metabolic Diseases, Pharmacology Research Labs., Astellas Pharma Inc. Division of Genetic Information, Institute for Genome Research, The University of Tokushima
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- Suzuki Takao
- Department of Functional Genomics, Molecular Medicine Research Labs., Astellas Pharma Inc. Division of Genetic Information, Institute for Genome Research, The University of Tokushima
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- Kitayama Susumu
- Department of Metabolic Diseases, Pharmacology Research Labs., Astellas Pharma Inc. Division of Genetic Information, Institute for Genome Research, The University of Tokushima
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- Moritani Maki
- Division of Genetic Information, Institute for Genome Research, The University of Tokushima
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- Inoue Hiroshi
- Division of Genetic Information, Institute for Genome Research, The University of Tokushima
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- Itakura Mitsuo
- Division of Genetic Information, Institute for Genome Research, The University of Tokushima Setagaya Memorial Hospital
書誌事項
- タイトル別名
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- <i>Bhlhe40</i>, a potential diabetic modifier gene on <i>Dbm1</i> locus, negatively controls myocyte fatty acid oxidation
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We have previously identified significant quantitative trait loci (QTL) Dbm1 (diabetic modifier QTL 1) on chromosome 6, affecting plasma glucose and insulin concentrations and body weight on F2 progeny of hypoinsulinemic diabetic Akita mice, with the heterozygous Ins2 gene Cys96Tyr mutation, and non-diabetic A/J mice. To discover diabetic modifier genes on Dbm1, we constructed congenic strain for Dbm1 using the Akita allele as donor in A/J allele genetic background, and compared diabetes-related phenotypes to control mice. The homozygote for Akita allele of Dbm1 was associated with lower plasma glucose concentrations in glucose tolerance test (GTT) in the hypoinsulinemic condition derived from the Ins2 mutation and lower plasma insulin concentrations and body weight in the normoinsulinemic condition without the Ins2 mutation than the homozygote for A/J allele, as we performed QTL analysis on F2 intercross mice. The Akita allele also decreased the epididymal white adipose tissue (EWAT) weight. According to the analysis of sub-congenic strains, we narrowed down the responsible diabetic modifier region to 9 Mb. As fourteen candidate genes exist in this region, we analyzed genomic variants of these genes and gene expression in the muscle, liver, and EWAT and identified that Bhlhe40 gene expression in muscle is decreased in congenic mice. According to the in vitro functional analyses, Bhlhe40 was shown to negatively control fatty acid oxidation in cultured myocyte. Based on these, we conclude that Bhlhe40 is a possible candidate diabetic modifier gene responsible for Dbm1 locus affecting diabetes and/or obesity through negatively controlling fatty acid oxidation in muscle.
収録刊行物
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- Genes & Genetic Systems
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Genes & Genetic Systems 87 (4), 253-264, 2012
日本遺伝学会
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詳細情報 詳細情報について
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- CRID
- 1390282680449329152
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- NII論文ID
- 10031126618
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- NII書誌ID
- AA11077421
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- COI
- 1:STN:280:DC%2BC3s3htFOlsQ%3D%3D
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- ISSN
- 18805779
- 13417568
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- NDL書誌ID
- 024078309
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- PubMed
- 23229312
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可