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動脈粥樣硬化模型

ApoE敲除小鼠(ApoE-deificient mouse)

ApoE基因敲除或沉默小鼠

動脈粥樣硬化造模和模型飼料



ApoE基因敲除小鼠動脈粥樣硬化模型的造模和復制方法
Atherosclerosis Model in ApoE-knockout Mouse

一、ApoE敲除小鼠或大鼠常用模型飼料


在載脂蛋白E(apolipoprotein E, ApoE)敲除的小鼠或大鼠,除非研究特殊,一般采用以下兩類模型飼料之一:

♥ 高脂高膽固醇模型飼料;

♥ 高膽固醇飼料。

至于選擇以上哪一種造模飼料,取決于研究目的和需要。

如果希望研究的是高脂肪高膽固醇飲食與動脈粥樣硬化的關系,或者,研究的是實驗干預(如,藥物或食品功能因子)對動脈粥樣硬化形成或發展的預防或治療作用涉及飲食脂肪和膽固醇,則應該考慮高脂肪高膽固醇模型飼料。

如果希望研究的是飲食膽固醇與動脈粥樣硬化的關系,或者,希望建立的飲食膽固醇所致的動脈粥樣硬化,則選擇高膽固醇飼料。

二、ApoE敲除小鼠或大鼠的年齡和造模時間


采用的ApoE敲除動物的年齡不限,取決于研究目的和需要。但要注意以下方面:

(1)要與臨床相結合。雖然可以從幼年期開始進行造模,但是,要考慮到臨床病人動脈粥樣硬化發生的年齡,從而根據動物相應的年齡開始造模。一般文獻中采用6-8周齡。

(2)要與動物機能的狀態相結合。ApoE敲除鼠不僅自發發生動脈粥樣硬化,而且免疫系統以及皮膚等部位異常,超過15月齡已經有很高的死亡率。因此,如果研究老齡與動脈粥樣硬化的關系,或者觀察動脈粥樣硬化隨著年齡發生改變的關系,或者研究動脈粥樣硬化與老齡癡呆(AD),15個月齡是上限。

三、購買ApoE小鼠或大鼠和喂養飼料注意事項


無論是批次購買,還是引種自繁育,都應當注意對基因敲除進行確認性檢測。這是使用基因工程動物的常規和必備的工作。

ApoE敲除動物的喂養與普通大小鼠的喂養相同,但是,飼料質量非常關鍵,一般大小鼠飼料日糧中含有大量影響動物機能的因素,因此不是理想的喂養飼料。建議采用南通特洛菲飼料科技有限公司LAD0011號飼料。

四、注意ApoE敲除的大鼠和小鼠的區別


雖然都是敲除ApoE,但是,其母本差別往往較大。在小鼠,常用的是C57BL/6小鼠為母本進行ApoE敲除,而大鼠一般是在SD大鼠上進行。由于C57BL/6小鼠是一種對脂質代謝有較高敏感的肥胖傾向的小鼠,與SD大鼠有較大的區別。一般來說,由于ApoE基因敲除大鼠的壽命短,不主張采用高脂模型飼料長期喂養的方法進行造模。

References:

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Kim MJ, Moon MK, Kang GH, Lee KJ, Choi SH, Lim S, Oh BC, Park DJ, Park KS, Jang HC, Park YJ. Chronic Exposure to Bisphenol A can Accelerate Atherosclerosis in High-Fat-Fed Apolipoprotein E Knockout Mice. Cardiovasc Toxicol. 2013 Nov 14.

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Lu T, Wen S, Cui Y, Ju SH, Li KC, Teng GJ. Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome. Int J Cardiovasc Imaging. 2014 Jan;30(1):221-31.

Wu X, Balu N, Li W, Chen Y, Shi X, Kummitha CM, Yu X, Yuan C, Lu ZR. Molecular MRI of atherosclerotic plaque progression in an ApoE(-/-) mouse model with a CLT1 peptide targeted macrocyclic Gd(III) chelate. Am J Nucl Med Mol Imaging. 2013 Sep 19;3(5):446-55.

Hurt-Camejo E, Gautier T, Rosengren B, Dikkers A, Behrendt M, Grass DS, Rader DJ, Tietge UJ. Expression of type IIA secretory phospholipase A2 inhibits cholesteryl ester transfer protein activity in transgenic mice. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2707-14.

Bigalke B, Phinikaridou A, Andia ME, Cooper MS, Schuster A, Sch?nberger T, Griessinger CM, Wurster T, Onthank D, Ungerer M, Gawaz M, Nagel E, Botnar RM. Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc. Circ Cardiovasc Imaging. 2013 Nov;6(6):957-64.

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Shin IJ, Shon SM, Schellingerhout D, Park JY, Kim JY, Lee SK, Lee DK, Lee HW, Ahn BC, Kim K, Kwon IC, Kim DE.Characterization of partial ligation-induced carotid atherosclerosis model using dual-modality molecular imaging in ApoE knock-out mice. PLoS One. 2013 Sep 12;8(9):e73451.

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Guo YQ, Li YF, Wang ZH. Effects of β?-adrenoceptor on scavenger receptor class B type 1 and its signal transduction pathway in apolipoprotein E knockout mice. Eur J Pharmacol. 2013 Aug 15;714(1-3):295-302.

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Kawahito H, Yamada H, Irie D, Kato T, Akakabe Y, Kishida S, Takata H, Wakana N, Ogata T, Ikeda K, Ueyama T, Matoba S, Mori Y, Matsubara H. Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE-/- mice. Am J Physiol Heart Circ Physiol. 2013 Sep 1;305(5):H667-75.

Heinonen SE, Kivel? AM, Huusko J, Dijkstra MH, Gurzeler E, M?kinen PI, Lepp?nen P, Olkkonen VM, Eriksson U, Jauhiainen M, Yl?-Herttuala S. The effects of VEGF-A on atherosclerosis, lipoprotein profile, and lipoprotein lipase in hyperlipidaemic mouse models. Cardiovasc Res. 2013 Sep 1;99(4):716-23.

Auvinen HE, Wang Y, Princen H, Romijn JA, Havekes LM, Smit JW, Meijer OC, Biermasz NR, Rensen PC, Pereira AM. Both transient and continuous corticosterone excess inhibit atherosclerotic plaque formation in APOE*3-leiden.CETP mice. PLoS One. 2013 May 22;8(5):e63882.

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Zhang Y, Li L, You J, Cao J, Fu X. Effect of 7-difluoromethyl-5, 4'-dimethoxygenistein on aorta atherosclerosis in hyperlipidemia ApoE(-/-) mice induced by a cholesterol-rich diet. Drug Des Devel Ther. 2013 Apr 3;7:233-42.

Richez C, Richards RJ, Duffau P, Weitzner Z, Andry CD, Rifkin IR, Aprahamian T. The effect of mycophenolate mofetil on disease development in the gld.apoE (-/-) mouse model of accelerated atherosclerosis and systemic lupus erythematosus. PLoS One. 2013;8(4):e61042.

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Burris RL, Ng HP, Nagarajan S. Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-κB and AKT signaling pathway in apolipoprotein E-deficient mice. Eur J Nutr. 2014 Feb;53(1):135-48.

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Huang Q, Qin L, Dai S, Zhang H, Pasula S, Zhou H, Chen H, Min W. AIP1 suppresses atherosclerosis by limiting hyperlipidemia-induced inflammation and vascular endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2013 Apr;33(4):795-804.

Cuerrier CM, Chen YX, Tremblay D, Rayner K, McNulty M, Zhao X, Kennedy CR, de BelleRoche J, Pelling AE, O'Brien ER. Chronic over-expression of heat shock protein 27 attenuates atherogenesis and enhances plaque remodeling: a combined histological and mechanical assessment of aortic lesions. PLoS One. 2013;8(2):e55867.

Ruotsalainen AK, Inkala M, Partanen ME, Lappalainen JP, Kansanen E, M?kinen PI, Heinonen SE, Laitinen HM, Heikkil? J, Vatanen T, H?rkk? S, Yamamoto M, Yl?-Herttuala S, Jauhiainen M, Levonen AL. The absence of macrophage Nrf2 promotes early atherogenesis. Cardiovasc Res. 2013 Apr 1;98(1):107-15.

Tissot AC, Spohn G, Jennings GT, Shamshiev A, Kurrer MO, Windak R, Meier M, Viesti M, Hersberger M, Kündig TM, Ricci R, Bachmann MF. A VLP-based vaccine against interleukin-1α protects mice from atherosclerosis. Eur J Immunol. 2013 Mar;43(3):716-22.

Liu C, Desikan R, Ying Z, Gushchina L, Kampfrath T, Deiuliis J, Wang A, Xu X, Zhong J, Rao X, Sun Q, Maiseyeu A, Parthasarathy S, Rajagopalan S. Effects of a novel pharmacologic inhibitor of myeloperoxidase in a mouse atherosclerosis model. PLoS One. 2012;7(12):e50767.

Campbell IC, Weiss D, Suever JD, Virmani R, Veneziani A, Vito RP, Oshinski JN, Taylor WR. Biomechanical modeling and morphology analysis indicates plaque rupture due to mechanical failure unlikely in atherosclerosis-prone mice. Am J Physiol Heart Circ Physiol. 2013 Feb 1;304(3):H473-86.

Wan W, Lionakis MS, Liu Q, Roffê E, Murphy PM. Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice. Cardiovasc Res. 2013 Mar 1;97(3):580-8.

Boldt HB, Bale LK, Resch ZT, Oxvig C, Overgaard MT, Conover CA. Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic lesion development in mice. Endocrinology. 2013 Jan;154(1):246-52.

McCarthy C, Duffy MM, Mooney D, James WG, Griffin MD, Fitzgerald DJ, Belton O. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J. 2013 Feb;27(2):499-510.

Merino H, Parthasarathy S, Singla DK. Partial ligation-induced carotid artery occlusion induces leukocyte recruitment and lipid accumulation--a shear stress model of atherosclerosis. Mol Cell Biochem. 2013 Jan;372(1-2):267-73.

Harada N, Ito K, Hosoya T, Mimura J, Maruyama A, Noguchi N, Yagami K, Morito N, Takahashi S, Maher JM, Yamamoto M, Itoh K. Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation. Free Radic Biol Med. 2012 Dec 15;53(12):2256-62.



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ApoE基因敲除小鼠其他疾病模型復制與模型飼料

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