Development of consomic mouse model for metabolic syndrome

代谢综合征小鼠模型的建立

• 批准号: 19300143
• 负责人: SUGIYAMA Fumihiro
• 金额: $ 12.23万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19300143/
• 关键词: NZOマウス; 量的形質遺伝子座; 高血圧; 肥満; 糖尿病; メタボリックシンドローム; 疾患モデル; マウス; コンソミック; QTL; メタポリックシンドローム

The development of metabolic syndrome is found in NZO/HILtJ mice, but not in C3H/HeJ mice. We identified quantitative trait loci associated with obesity, abnormal glucose metabolism and hypertension. To develop the animal model for understanding the molecular mechanism of metabolic syndrome, we successfully produced three consomic mouse strains, NZO/HILtJ-Chr 7^<C3H/HeJ,>, NZO/HILtJ-Chr 12^<C3H/HeJ> and NZO/HILtJ-Chr 17^<C3H/HeJ>. There were no significant differences in obesity, glucose metabolism and blood pressure between the consomic mice and NZO/HILtJ mice. These results demonstrate that a single major gene associated with metabolic syndrome was not located on the chromosome 7, 12 and 17 of NZO/HILtJ mice. Furthermore, we found Fgf5-deficient natural mutant mice from ICR mouse colony supporting the breeding of NZO/HILtJ mice. The Fgf5-decifient mice might be useful animal model for the basic research of hypertension and metabolic syndrome, because there is strong significant association between hypertension and Fgf5 polymorphism in human.

NZO/HILtJ小鼠出现代谢综合征，但C3 H/HeJ小鼠未出现代谢综合征。我们确定了与肥胖、糖代谢异常和高血压相关的数量性状位点。为建立代谢综合征分子机制的动物模型，我们成功地建立了NZO/HILtJ-Chr 7^<C3 H/HeJ>、NZO/HILtJ-Chr 12^<C3 H/HeJ>和NZO/HILtJ-Chr 17^<C3 H/HeJ>三种小鼠品系。正常小鼠与NZO/HILtJ小鼠在肥胖、糖代谢和血压方面无显著差异。这些结果表明，与代谢综合征相关的单个主基因不位于NZO/HILtJ小鼠的7、12和17号染色体上。此外，我们从ICR小鼠群体中发现了Fgf 5缺陷型自然突变小鼠，支持NZO/HILtJ小鼠的育种。Fgf 5基因多态性与人类高血压的发生有密切的相关性，因此Fgf 5基因敲除小鼠可能成为高血压和代谢综合征基础研究的动物模型。

项目成果

(NZOxC#H)F2マウスにおける血圧量的形質遺伝子座解析

(NZOxCH)F2 小鼠血压数量性状基因座分析

• 发表时间: 2007
• 作者: 西原絵里;ら
• 通讯作者: ら

Deterioration of atherosclerosis in mice lacking angiotensin II type 1A receptor in bone marrow-derived cells

• DOI: 10.1038/labinvest.2008.42
• 发表时间: 2008-07-01
• 期刊: LABORATORY INVESTIGATION
• 影响因子: 5
• 作者: Kato, Hideki;Ishida, Junji;Fukamizu, Akiyoshi
• 通讯作者: Fukamizu, Akiyoshi

メタボリックシンドロームを発症するNZOマウスにおける制限給餌の効果

限制喂养对出现代谢综合征的 NZO 小鼠的影响

• 发表时间: 2009
• 作者: 石毛太一郎;西野入燈;國田智;杉山文博;八神健一
• 通讯作者: 八神健一

Genetic analysis of blood pressure in 8 mouse intercross populations.

• DOI: 10.1161/hypertensionaha.109.134569
• 发表时间: 2009-10
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Feng M;Deerhake ME;Keating R;Thaisz J;Xu L;Tsaih SW;Smith R;Ishige T;Sugiyama F;Churchill GA;DiPetrillo K
• 通讯作者: DiPetrillo K

Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ x C3H/HeJ intercrosses

• DOI: 10.1007/s00335-007-9033-5
• 发表时间: 2007-08-01
• 期刊: MAMMALIAN GENOME
• 影响因子: 2.5
• 作者: Nishihara, Eri;Tsaih, Shirng-Wern;Sugiyama, Fumihiro
• 通讯作者: Sugiyama, Fumihiro