Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

Watanabe TK; Okuno S; Ono T; Yamasaki Y; Oga K; Mizoguchi-Miyakita A; Miyao H; Suzuki M; Momota H; Goto Y; Shinomiya H; Hishigaki H; Hayashi I; Asai T; Wakitani S; Takagi T; Nakamura Y; Tanigami A

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Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

机译：在同基因动物中，Dmo1基因座的单等位基因校正显着减弱了OLETF大鼠的肥胖，血脂异常和糖尿病表型。

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1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

机译：1.全基因组扫描已将Dmo1确定为大冢长埃文斯德岛肥胖（OLETF）大鼠血脂异常和肥胖的主要定量性状基因座。 2.通过与糖尿病OLETF大鼠进行连续回交育种，我们已经为Dmo1基因座生产了同基因大鼠。应用了标记辅助的速度同基因实验方案，可以将非糖尿病布朗挪威（BN）大鼠的染色体片段有效地转移到OLETF背景中。 3.在第四代同类动物中，我们观察到Dmo1基因座对脂质代谢，肥胖控制和血浆葡萄糖稳态具有实质性的治疗作用。 4.我们得出的结论是，Dmo1在禁食时主要影响脂质稳态，肥胖控制和/或葡萄糖稳态，其次是在加载后参与葡萄糖稳态。 5.本研究结果表明，尽管II型糖尿病综合征具有复杂的多基因性质，但对Dmo1基因座遗传缺陷进行单等位基因校正仍可产生实质性的治疗效果。

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《Clinical and experimental pharmacology & physiology》 |2001年第2期|共15页
作者
Watanabe TK; Okuno S; Ono T; Yamasaki Y; Oga K; Mizoguchi-Miyakita A; Miyao H; Suzuki M; Momota H; Goto Y; Shinomiya H; Hishigaki H; Hayashi I; Asai T; Wakitani S; Takagi T; Nakamura Y; Tanigami A;
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正文语种 eng
中图分类药理学;
关键词
Blood Glucose; Body Weight; Chromosome Mapping; Diabetes Mellitus; Non-Insulin-Dependent; 血糖; 体重; 染色体图; 糖尿病; 非胰岛素依赖型; 高脂血症; 肥胖症;

机译：Blood Glucose;Body Weight;Chromosome Mapping;Diabetes Mellitus;Non-Insulin-Dependent;血糖;体重;染色体图;糖尿病;非胰岛素依赖型;高脂血症;肥胖症;

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1. Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat. [J] . Watanabe TK, Okuno S, Ono T, Clinical and experimental pharmacology & physiology . 2001,第1a2期

机译：在同基因动物中，Dmo1基因座的单等位基因校正显着减弱了OLETF大鼠的肥胖，血脂异常和糖尿病表型。
2. A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats. [J] . Tanigami A Clinical and experimental pharmacology & physiology . 2004,第1a2期

机译：小于1.7 cM的时间间隔是OLETF大鼠Dmo1肥胖表型的原因。
3. Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat. [J] . Watanabe A, Okuno S, Okano M, Brain research . 2007,第0期

机译：糖尿病OLETF 1型同系大鼠的情绪行为发生了改变。
4. Confluence of Genes Related to the Combined Etiology DOISm (Diabetes, Obesity, Inflammation and Metabolic Syndrome) in Dissecting Nutritional Phenotypes [C] . Ana Paula Moreira Bezerra, Samara Cardoso Silva-Santiago, Jose Francisco Diogo Da Silva Jr., International Conference on Bioinformatics and Biomedical Engineering . 2016

机译：解剖营养表型与病原学DOISm（糖尿病，肥胖，炎症和代谢综合症）相关基因的融合
5. Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study. [D] . Barroso, Cristina Sofia. 2005

机译：肥胖症和perilipin基因：在社区动脉粥样硬化风险研究中，单基因座和多基因座变异，肥胖相关的定量性状和疾病相关的表型的作用。
6. Infection-dependent phenotypes in MHC-congenic mice are not due to MHC: can we trust congenic animals? [O] . Erin E McClelland, Kristy Damjanovich, Kyle Gardner, 2004

机译：MHC基因小鼠的感染依赖表型不是MHC引起的：我们可以相信同类动物吗？
7. Identification of a Quantitative Trait Locus Influencing Plasma Insulin Levels after 70 Pancreatectomy Using the OLETF Rat. [O] . Daniel H. MORALEJO, Tomoe OGINO, Min ZHU, 1998

机译：用OLETF大鼠鉴定影响70％胰腺切除术后的血浆胰岛素水平的定量性状基因座。

Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

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