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關(guān)鍵詞:多發(fā)性硬化癥,Multiple sclerosis,EAE,MOG, MOG35-55,PLP,PLP (139-151),實驗性自身免疫性腦脊髓炎
多發(fā)性硬化癥(Multiple sclerosis (MS))/實驗性自身免疫性腦脊髓炎模型(EAE)研究專題
背景介紹
多發(fā)性硬化癥(multiple sclerosis, MS)是一種原發(fā)于中樞神經(jīng)系統(tǒng)的炎癥性脫髓鞘疾病。MS確切的發(fā)病機制雖尚不清楚, 但普遍認為是在易感基因的基礎(chǔ)上, 受環(huán)境因素觸發(fā), 由CD4+ T細胞介導(dǎo)的中樞神經(jīng)系統(tǒng)(central nervous system, CNS)自身免疫性疾病。實驗性自身免疫性腦脊髓炎(experimental autoimmune encephalomyelitis, EAE)是一種以特異性致敏的CD4+ T細胞介導(dǎo)為主, 對實驗動物進行髓鞘蛋白免疫構(gòu)建的疾病模型。EAE與人類MS在臨床、生化、免疫及病理等諸多方面具有相同的特征, 所以它是目前*的 MS理想動物模型。
(一)慢性EAE(Chronic EAE)模型的建立
髓鞘少突膠質(zhì)細胞糖蛋白(MOG) 是髓鞘膜和少突膠質(zhì)細胞表面zui外層的膜蛋白,是導(dǎo)致多發(fā)性硬化(MS)脫髓鞘的關(guān)鍵成分,針對MOG的抗體能夠在體內(nèi)和體外造成脫髓鞘。MOG數(shù)量較少,約占髓鞘蛋白總量的0.01%-0.05%,具有高度免疫原性,它直接參與CNS的體液免疫反應(yīng),是引起實驗性自身免疫性腦脊髓炎(EAE)中脫髓鞘的主要免疫靶點。MOG 35-55含21個氨基酸,是*既能引起脫髓鞘抗體反應(yīng)又能引起T細胞反應(yīng)的中樞神經(jīng)系統(tǒng)髓鞘蛋白成分。MOG 35-55可在C57BL/6小鼠體內(nèi)誘導(dǎo)MOG35-55/I-Ab特異性自身反應(yīng)性CD4+T細胞異常活化,誘發(fā)EAE。
產(chǎn)品性質(zhì)
英文名稱 | Myelin Oligodendrocyte Glycoprotein(35-55) |
CAS No | 149635-73-4 |
多肽序列 | Met-Glu-Val-Gly-Trp-Tyr-Arg-Ser-Pro-Phe-Ser-Arg-Val-Val-His-Leu-Tyr-Arg-Asn-Gly-Lys (MEVGWYRSPFSRVVHLYRNGK) |
分子式 | C118H177N35O29S |
分子量 | 2582.01 |
外觀 | 白色粉末 |
純度 | 98.68% |
溶解性 | 溶于水 |
運輸與保存方法
冰袋(wet ice)運輸。收到產(chǎn)品后放到-20 oC保存,保持干燥。不建議溶液狀態(tài)保存。
產(chǎn)品信息
產(chǎn)品編號 | 產(chǎn)品名稱 | 規(guī)格 | 價格(元) |
20603ES03 | Myelin Oligodendrocyte Glycoprotein(35-55) 髓鞘少突膠質(zhì)細胞糖蛋白MOG (35-55) | 1mg | 1790.00 |
Q&A
1. 如何選擇模型動物?
答:一般選擇雌性C57BL/6小鼠,10-14周左右。
2.在什么部位注射?每次注射的量?
皮下注射,每只小鼠200μg MOG 35-55多肽。
參考文獻
1.Mandy?L. Ford, et al. An MHC anchor-substituted analog of myelin oligodendrocyte glycoprotein?35–55 induces IFN-γ and autoantibodies in the absence of experimental autoimmune encephalomyelitis and optic neuritis. European Journal of Immunology Volume 34, Issue 2, pages 388–397,February 2004
2.Cathleen Rich, et al. Myelin oligodendrocyte glycoprotein-35–55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. Eur. J. Immunol. 2004. 34: 1251–1261
3.Cong-Qiu Chu, et al. Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon γ–Deficient Mice Leads to Exacerbation of Experimental Autoimmune Encephalomyelitis. JEM Home 2000 Archive 3 July Chu et al. 192 (1): 123.
4. Stefanie Kuerten, et al. MP4- and MOG:35–55-induced EAE in C57BL/6 mice differentially targets brain, spinal cord and cerebellum. Journal of Neuroimmunology Volume 189, Issues 1–2, 2007 (31–40).
5. Anthony Slavin, et al. Induction of a Multiple Sclerosis-Like Disease in Mice with an Immunodominant Epitope of Myelin Oligodendrocyte Glycoprotein. 1998, Vol. 28, No. 2 , 109-120.
6. McFarland, H. F., et al. Multiple sclerosis: a complicated picture of autoimmunity. Nat. Immunol. 8, 913-919, doi:10.1038/ni1507
(2007).
7. Wiendl, H. Neuroinflammation: the world is not enough. Curr. Opin. Neurol. 25, 302-305, doi:10.1097/WCO.0b013e3283534abf (2012).
8. van der Star, B. J. et al. In vitro and in vivo models of multiple sclerosis. CNS Neurol. Disord. Drug Targets. 11, 570-588 (2012).
9. Pachner, A. R. Experimental models of multiple sclerosis. Curr. Opin. Neurol. 24, 291-299, doi:10.1097/WCO.0b013e328346c226 (2011).
10. Bittner, S. et al. The TASK1 channel inhibitor A293 shows efficacy in a mouse model of multiple sclerosis. Exp. Neurol. 238, 149-155, doi:10.1016/j.expneurol.2012.08.021 (2012).
(二)復(fù)發(fā)-緩解型EAE(Relapsing- Remitting EAE)模型的建立
復(fù)發(fā)-緩解型MS是人類多發(fā)性硬化(MS)zui常見的一種,這類型的疾病與PLP139-151/CFA誘導(dǎo)的SJL小鼠EAE癥狀zui為相似,因此,這是一種常用于研究藥物對復(fù)發(fā)型EAE作用的模型。而且,該模型也表現(xiàn)出較高的EAE同步發(fā)病率。復(fù)發(fā)-緩解型EAE常用于MS治療,以研究EAE復(fù)發(fā)的進展情況。Proteolipid Protein (PLP)是一種高度疏水的膜蛋白,是中樞神經(jīng)系統(tǒng)(central nervous system, CNS)中含量zui多的髓磷脂。與IAS MHCII結(jié)合時,PLP 139–151和PLP 178–191具有相同的高親和力,但是,免疫系統(tǒng)對PLP 139–151表位產(chǎn)生的免疫反應(yīng)是主要的。對于PLP誘導(dǎo)的EAE模型,SJL (H-2s)小鼠具有很高的致敏性。
產(chǎn)品性質(zhì)
英文名稱 | Proteolipid Protein (PLP) (139-151) |
CAS No | 122018-58-0 |
多肽序列 | H - His - Cys - Leu - Gly - Lys - Trp - Leu - Gly - His - Pro - Asp - Lys - Phe – OH (HSLGKWLGHPDKF) |
分子式 | C72H104N20O17 |
分子量 | 1521.47 |
外觀 | 白色粉末 |
純度 | ≥ 95%(HPLC) |
溶解性 | 溶于水(2 mg/ml) |
運輸與保存方法
冰袋(wet ice)運輸。收到產(chǎn)品后放到-20 oC保存,保持干燥。不建議溶液狀態(tài)保存。
產(chǎn)品信息
產(chǎn)品編號 | 產(chǎn)品名稱 | 規(guī)格 | 價格(元) |
20627ES03 | PLP(Proteolipid Protein 139-151) | 1mg | 1658.00 |
Direct EAE induction in SJL mice
Q&A
1. 如何選擇模型動物?
答:一般選擇雌性SJL小鼠,9-10周左右。
2.在什么部位注射?每次注射的量?
皮下注射,每只小鼠100μg PLP139-151 。
參考文獻
1. McRae BL, et al. Differential recognition of peptide analogs by naive verses activated PLP 139-151-specific CD4+ T cells. J Neuroimmunol. 1995 Jul;60(1-2):17-28.
2. Ana C. Anderson, et al. High Frequency of Autoreactive Myelin Proteolipid Protein–Specific T Cells in the Periphery of Naive Mice. JEM vol. 191 (5): 761-770.
3. Maria Katsara, et al. Immune responses of linear and cyclic PLP139-151 mutant peptides in SJL/J mice: peptides in their free state versus mannan conjugation. Immunotherapy, 6(6): 709-724. DOI 10.2217/imt.14.42
4. Stephen D. Miller, et al. Experimental Autoimmune Encephalomyelitis in the Mouse. Curr Protoc Immunol. 2007 May ; CHAPTER: Unit–15.1. doi:10.1002/0471142735.im1501s77.
5. Hanspeter Waldner, et al. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor. PNAS March 28, 2000 97(7) 3412–3417.
6. By Ana C. Anderson, et al. High Frequency of Autoreactive Myelin Proteolipid Protein–specific T Cells in the Periphery of Naive Mice: Mechanisms of Selection of the Self-reactive Repertoire. J. Exp. Med. 191(5) 2000: 761–770.
7. Harald H. Hofstetter, et al. Pertussis Toxin Modulates the Immune Response to Neuroantigens Injected in Incomplete Freund’s Adjuvant: Induction of Th1 Cells and Experimental Autoimmune Encephalomyelitis in the Presence of High Frequencies of Th2 Cells. J Immunol 2002; 169:117-125.