人感染H3N2流感病毒后，症状与普通人流感相似，临床表现包括发热（病毒感染发热一般是持续的，但下午较其他时间温度要高）、咳嗽、喉咙痛、身体疼痛、头痛、发冷和疲劳等，有些还会出现腹泻和呕吐，重者会继发肺炎和呼吸衰竭，甚至死亡。H3N2流感病毒传播速度快，人体对新变异病毒没有天然抗体。一般通过打喷嚏、咳嗽和物理接触方式传播。感染病毒的患者以青壮年为主，大多数年龄在25岁至45岁之间。 由于个人免疫情况不一样，年轻人、儿童感染后，更容易出现流感样的症状，体温超过38℃，全身肌肉酸痛。老年人的反应就不会那么强烈，好多老年人感染后体温就不会很高，机体反应没有儿童敏感。 目前为广大学者接受的H3N2流感病毒致病机制主要有如下几种：①病毒诱导宿主细胞产生凋亡是其致细胞病变的重要机理之一；②病毒感染后对细胞造成的氧化应激损伤也是学者普遍接受的致病机制；③细胞因子风暴学说等其他学术学说和理论。以上3 种机制相互联系，并且均与凋亡密切相关。 流感病毒感染机体后，可损害呼吸道上皮、肺上皮细胞，也可损伤肺外器官。不管在体内或体外流感病毒都可诱导宿主细胞凋亡，流感病毒诱导细胞凋亡可能是通过多条途径实现的，各条途径又互相联系，参与成分既有病毒的，也有细胞成分。整个过程由于多种细胞因子及病毒蛋白的参与而变得错综复杂。病毒感染引起宿主细胞凋亡损害宿主，但另一方面，宿主也通过这一方式限制病毒在机体内的增殖和扩散。病毒感染细胞后，若细胞迅速发生凋亡，则不利于病毒的繁殖。

病毒株为A/Brisbane/10/07 (H3N2)，雪貂经轻度麻醉后滴鼻感染H3N2病毒。实验的观察期为5天。皮下植入体温芯片用于监测体温、体重变化。每日观察雪貂临床症变化，在感染后第5天安乐动物，取组织样本用于监测病毒复制动力曲线和动物感染后组织炎症反应检查。

1.鲍琳琳，占玲俊，秦川等.雪貂感染流感病毒H3N2动物模型的建立[J]，中国比较医学杂志,2011,21(8):5-9.

免疫系统相关疾病

胚胎干细胞打靶

1.Kimura T et al. Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies. Genes Cells. 1996 Jan;1(1):115-24.  

免疫系统相关疾病

转基因小鼠，由MHC II启动子驱动T细胞受体链基因。

[1]Zhou P, Borojevic R, Streutker C, Snider D, Liang H, Croitoru K. Expression of dual TCR on DO11.10 T cells allows for ovalbumin-induced oral tolerance to prevent T cell-mediated colitis directed against unrelated enteric bacterial antigens. J Immunol. 2004 Feb 1;172(3):1515-23. doi: 10.4049/jimmunol.172.3.1515. PMID: 14734729. [2]Kusuhara M, Matsue K, Edelbaum D, Loftus J, Takashima A, Matsue H. Killing of naive T cells by CD95L-transfected dendritic cells (DC): in vivo study using killer DC-DC hybrids and CD4(+) T cells from DO11.10 mice. Eur J Immunol. 2002 Apr;32(4):1035-43. doi: 10.1002/1521-4141(200204)32:4<1035::AID-IMMU1035>3.0.CO;2-7. PMID: 11920570.

B6.Cg-Tg(TcraTcrb)425-

从包含内源性TCR启动子的T细胞杂交瘤克隆中提取含有T细胞受体α链和β链的转基因结构被共注射到受精卵中。

1Barnden MJ; Allison J; Heath WR; Carbone FR.. Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol，1998，76(1):34-40. 2Parameswaran N; Samuvel DJ; Kumar R; Thatai S; Bal V; Rath S; George A.. Oral tolerance in T cells is accompanied by induction of effector function in lymphoid organs after systemic immunization. Infect Immun，2004，72(7):3803-11. 3Abboud G; Staumont-Salle D; Kanda A; Roumier T; Deruytter N; Lavogiez C; Fleury S; Remy P; Papin JP; Capron M; Dombrowicz D.. Fc(epsilon)RI and FcgammaRIII/CD16 differentially regulate atopic dermatitis in mice. J Immunol，2009，182(10):6517-26. 4Abou Fakher FH; Rachinel N; Klimczak M; Louis J; Doyen N.. TLR9-dependent activation of dendritic cells by DNA from Leishmania major favors Th1 cell development and the resolution of lesions. J Immunol，2009，182(3):1386-96.

免疫系统相关疾病

胚胎干细胞打靶

1Martin-Orozco N; Chen Z; Poirot L; Hyatt E; Chen A; Kanagawa O; Sharpe A; Mathis D; Benoist C. Paradoxical dampening of anti-islet self-reactivity but promotion of diabetes by OX40 ligand. J Immunol，2003，171(12):6954-60. 2Chen AI; McAdam AJ; Buhlmann JE; Scott S; Lupher ML Jr; Greenfield EA; Baum PR; Fanslow WC; Calderhead DM; Freeman GJ; Sharpe AH. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity，1999，11(6):689-98. 3Arestides RS; He H; Westlake RM; Chen AI; Sharpe AH; Perkins DL; Finn PW. Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation. Eur J Immunol，2002，32(10):2874-80.

免疫系统相关疾病

胚胎干细胞打靶

1Alexopoulou L; Holt AC; Medzhitov R; Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732-8. 2Hoebe K; Janssen EM; Kim SO; Alexopoulou L; Flavell RA; Han J; Beutler B. 2003. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol 4(12):1223-9. Aeffner F; Traylor ZP; Yu EN; Davis IC. 2011. Double-stranded RNA induces similar pulmonary dysfunction to respiratory syncytial virus in BALB/c mice. Am J Physiol Lung Cell Mol Physiol 301(1):L99-L109.

免疫系统相关疾病

胚胎干细胞打靶

1. Hogquist KA; Jameson SC; Heath WR; Howard JL; Bevan MJ; Carbone FR. 1994. T cell receptor antagonist peptides induce positive selection. Cell 76(1):17-27. 2.Chen W; Jin W; Tian H; Sicurello P; Frank M; Orenstein JM; Wahl SM. 2001. Requirement for transforming growth factor beta1 in controlling T cell apoptosis. J Exp Med 194(4):439-53. 3.Dillon S; Agrawal A; Van Dyke T; Landreth G; McCauley L; Koh A; Maliszewski C; Akira S; Pulendran B. 2004. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172(8):4733-43. 4.Geissmann F; Jung S; Littman DR. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71-82.

免疫系统相关疾病

胚胎干细胞打靶

1Hogquist KA; Jameson SC; Heath WR; Howard JL; Bevan MJ; Carbone FR. 1994. T cell receptor antagonist peptides induce positive selection. Cell 76(1):17-27. 2Chen W; Jin W; Tian H; Sicurello P; Frank M; Orenstein JM; Wahl SM. 2001. Requirement for transforming growth factor beta1 in controlling T cell apoptosis. J Exp Med 194(4):439-53. 3Dillon S; Agrawal A; Van Dyke T; Landreth G; McCauley L; Koh A; Maliszewski C; Akira S; Pulendran B. 2004. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 172(8):4733-43.

免疫系统相关疾病

胚胎干细胞打靶

1Finotto S; Neurath MF; Glickman JN; Qin S; Lehr HA; Green FH; Ackerman K; Haley K; Galle PR; Szabo SJ; Drazen JM; De Sanctis GT; Glimcher LH.. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science，2002，295(5553):336-8. 2Szabo SJ; Sullivan BM; Stemmann C; Satoskar AR; Sleckman BP; Glimcher LH.. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science，2002，295(5553):338-42. 3Albrecht I; Niesner U; Janke M; Menning A; Loddenkemper C; Kuhl AA; Lepenies I; Lexberg MH; Westendorf K; Hradilkova K; Grun J; Hamann A; Epstein JA; Chang HD; Tokoyoda K; Radbruch A.. Persistence of effector memory Th1 cells is regulated by Hopx. Eur J Immunol，2010，40(11):2993-3006. 4Alcaide P; Jones TG; Lord GM; Glimcher LH; Hallgren J; Arinobu Y; Akashi K; Paterson AM; Gurish MA; Luscinskas FW.. Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. J Exp Med，2007，204(2):431-9.

免疫系统相关疾病

胚胎干细胞打靶

1Belanger SD; St-Pierre Y. 2005. Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: implication of L-selectin in the growth of thymic lymphoma. Blood 105(12):4800-6. 2Eriksson EE. 2008. No detectable endothelial- or leukocyte-derived L-selectin ligand activity on the endothelium in inflamed cremaster muscle venules. J Leukoc Biol 84(1):93-103. 3Frenette PS; Mayadas TN; Rayburn H; Hynes RO; Wagner DD. 1996. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 84(4):563-74. Fujita T; Fujimoto M; Matsushita T; Shimada Y; Hasegawa M; Kuwano Y; Ogawa F; Takehara K; Sato S. 2007. Phase-Dependent Roles of E-Selectin during Chronic Contact Hypersensitivity Responses. Am J Pathol 170(5):1649-58.

传染病

克隆的人SCARB2基因插入到pXL-5载体的下游，由CMV启动子启动表达。

[1].Zhou D, Zhao Y, Kotecha A, Fry EE, Kelly JT, Wang X, Rao Z, Rowlands DJ, Ren J, Stuart DI. Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Nat Microbiol. 2019 Mar;4(3):414-419. doi: 10.1038/s41564-018-0319-z. Epub 2018 Dec 10. PMID: 30531980. [2].Zhang X, Yang P, Wang N, Zhang J, Li J, Guo H, Yin X, Rao Z, Wang X, Zhang L. The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection. Protein Cell. 2017 Aug;8(8):590-600. doi: 10.1007/s13238-017-0405-7. Epub 2017 Apr 26. PMID: 28447294; PMCID: PMC5546930.

传染病

本项目为了建立HCV感染的小鼠模型，克隆了人的SCARB1编码基因，将其插入pUBC载体的泛素基因启动子下游。

[1].Dreux M, Dao Thi VL, Fresquet J, Guérin M, Julia Z, Verney G, Durantel D, Zoulim F, Lavillette D, Cosset FL, Bartosch B. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains. PLoS Pathog. 2009 Feb;5(2):e1000310. doi: 10.1371/journal.ppat.1000310. Epub 2009 Feb 20. PMID: 19229312; PMCID: PMC2636890. Gao R, Gao W, Xu G, Xu J, Ren H. Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model. World J Gastroenterol. 2017 Jul 28;23(28):5158-5166. doi: 10.3748/wjg.v23.i28.5158. PMID: 28811710; PMCID: PMC5537182.