免疫系统相关疾病

胚胎干细胞打靶

[1].Jorgez CJ, Seth A, Wilken N, Bournat JC, Chen CH, Lamb DJ. E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling. Development. 2021 Jan 13;148(1):dev191189. doi: 10.1242/dev.191189. PMID: 33441379; PMCID: PMC7823160. Chen J, Zhu F, Weaks RL, Biswas AK, Guo R, Li Y, Johnson DG. E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks. Cell Cycle. 2011 Apr 15;10(8):1287-94. doi: 10.4161/cc.10.8.15341. PMID: 21512314; PMCID: PMC3117137.

免疫系统相关疾病

干细胞打靶

[1].Nicola NA; Robb L; Metcalf D; Cary D; Drinkwater CC; Begley CG.. Functional inactivation in mice of the gene for the interleukin-3 (IL-3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells. Blood，1996，87(7):2665-74. [2].Robb L; Drinkwater CC; Metcalf D; Li R; Kontgen F; Nicola NA; Begley CG.. Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5. Proc Natl Acad Sci U S A，1995，92(21):9565-9. [3].Scott CL; Robb L; Papaevangeliou B; Mansfield R; Nicola NA; Begley CG.. Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor. Blood，2000，96(4):1588-90.

传染病研究工具小鼠

克隆了人的CLDN1编码基因，将其插入pUBC载体的泛素基因启动子下游。

[1].Bekker V, Chanock SJ, Yeager M, Hutchinson AA, von Hahn T, Chen S, Xiao N, Dotrang M, Brown M, Busch MP, Edlin BR, Rice CM, O'Brien TR. Genetic variation in CLDN1 and susceptibility to hepatitis C virus infection. J Viral Hepat. 2010 Mar;17(3):192-200. doi: 10.1111/j.1365-2893.2009.01166.x. Epub 2009 Aug 7. PMID: 19674288; PMCID: PMC2921226. [2].Colpitts CC, Tawar RG, Mailly L, Thumann C, Heydmann L, Durand SC, Xiao F, Robinet E, Pessaux P, Zeisel MB, Baumert TF. Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape. Gut. 2018 Apr;67(4):736-745. doi: 10.1136/gutjnl-2016-312577. Epub 2017 Mar 30. PMID: 28360099; PMCID: PMC5868241.

传染病研究工具小鼠

克隆人的CD81编码基因，将其插入pUBC载体的泛素基因启动子下游。构建转基因小鼠

[1].Hadlock KG, Lanford RE, Perkins S, Rowe J, Yang Q, Levy S, Pileri P, Abrignani S, Foung SK. Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes. J Virol. 2000 Nov;74(22):10407-16. doi: 10.1128/jvi.74.22.10407-10416.2000. PMID: 11044085; PMCID: PMC110915. [2].Keck ZY, Li SH, Xia J, von Hahn T, Balfe P, McKeating JA, Witteveldt J, Patel AH, Alter H, Rice CM, Foung SK. Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity. J Virol. 2009 Jun;83(12):6149-60. doi: 10.1128/JVI.00248-09. Epub 2009 Mar 25. PMID: 19321602; PMCID: PMC2687388. [3].Rothwangl KB, Manicassamy B, Uprichard SL, Rong L. Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: putative CD81 binding region 1 is not involved in CD81 binding. Virol J. 2008 Mar 20;5:46. doi: 10.1186/1743-422X-5-46. PMID: 18355410; PMCID: PMC2277408.

免疫系统相关疾病

胚胎干细胞打靶

1Lindberg FP; Bullard DC; Caver TE; Gresham HD; Beaudet AL; Brown EJ. 1996. Decreased resistance to bacterial infection and granulocyte defects in IAP-deficient mice. Science 274(5288):795-8. 2Ball SL; Lindberg FP; Lagenaur CF; Peachey NS. 2001. Electroretinograms remain normal in mice lacking a synapse associated protein. Neurosci Lett 298(2):111-4. 3Beattie L; Svensson M; Bune A; Brown N; Maroof A; Zubairi S; Smith KR; Kaye PM. 2010. Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation. Eur J Immunol 40(1):117-23. 4Bouguermouh S; Van VQ; Martel J; Gautier P; Rubio M; Sarfati M. 2008. CD47 expression on T cell is a self-control negative regulator of type 1 immune response. J Immunol 180(12):8073-82. 5Capo C; Lindberg FP; Meconi S; Zaffran Y; Tardei G; Brown EJ; Raoult D; Mege JL. 1999. Subversion of monocyte functions by coxiella burnetii: impairment of the cross-talk between alphavbeta3 integrin and CR3. J Immunol 163(11):6078-85. 6Chang HP; Lindberg FP; Wang HL; Huang AM; Lee EH. 1999. Impaired memory retention and decreased long-term potentiation in integrin-associated protein-deficient mice. Learn Mem 6(5):448-57. 7Fortin G; Raymond M; Van VQ; Rubio M; Gautier P; Sarfati M; Franchimont D. 2009. A role for CD47 in the development of experimental colitis mediated by SIRPalpha+CD103- dendritic cells. J Exp Med 206(9):1995-2011.

免疫系统相关疾病，癌症

胚胎干细胞打靶

[1]Kuhn NF, Purdon TJ, van Leeuwen DG, Lopez AV, Curran KJ, Daniyan AF, Brentjens RJ. CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response. Cancer Cell. 2019 Mar 18;35(3):473-488.e6. doi: 10.1016/j.ccell.2019.02.006. PMID: 30889381; PMCID: PMC6428219.Zhang H, Cui Z, Cheng D, Du Y, Guo X, Gao R, Chen J, Sun W, He R, Ma X, Peng Q, Martin BN, Yan W, Rong Y, Wang C. RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis. Autophagy. 2021 Oct;17(10):3030-3047. doi: 10.1080/15548627.2020.1851496. Epub 2020 Dec 17. PMID: 33280498. [2]Ristov J, Espie P, Ulrich P, Sickert D, Flandre T, Dimitrova M, Müller-Ristig D, Weider D, Robert G, Schmutz P, Greutmann B, Cordoba-Castro F, Schneider MA, Warncke M, Kolbinger F, Cote S, Heusser C, Bruns C, Rush JS. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and non-depleting anti-CD40 monoclonal antibody. Am J Transplant. 2018 Dec;18(12):2895-2904. doi: 10.1111/ajt.14872. Epub 2018 May 24. PMID: 29665205.

免疫系统相关疾病

胚胎干细胞打靶

[1].Kinoshita K, Uemura M, Shimizu T, Kinoshita S, Marusawa H. Stepwise generation of AID knock-in and conditional knockout mice from a single gene-targeting event. Int Immunol. 2021 Jun 18;33(7):387-398. doi: 10.1093/intimm/dxab019. PMID: 33903914. [2].Galicia G, Lee DSW, Ramaglia V, Ward LA, Yam JY, Leung LYT, Li R, Handy M, Zhang J, Drohomyrecky PC, Lancaster E, Bar-Or A, Martin A, Gommerman JL. Isotype-Switched Autoantibodies Are Necessary To Facilitate Central Nervous System Autoimmune Disease in Aicda-/- and Ung-/- Mice. J Immunol. 2018 Aug 15;201(4):1119-1130. doi: 10.4049/jimmunol.1700729. Epub 2018 Jul 6. PMID: 29980612.

大鼠线粒体DNA G14098位点对应人体中线粒体DNA TRNE基因的G14710位点。临床上，线粒体DAN中14710位点的G突变为A能够导致线粒体肌病。

针对线粒体DNA G14098位点设计构建DdCBE载体，利用显微注射将DdCBE工具导入大鼠受精卵，然后移植到假孕大鼠中（见下图）。

Qi, X., Chen, X., Guo, J. et al. Precision modeling of mitochondrial disease in rats via DdCBE-mediated mtDNA editing. Cell Discov 7, 95 (2021).

大鼠线粒体DNA G7755位点对应人体中线粒体DNA TRNK基因的G8363位点。临床上，线粒体DNA中7755位点的G突变为A能够导致MERRF、心肌病和Leigh综合征等疾病。

针对线粒体DNA G7755位点设计构建DdCBE载体，利用显微注射将DdCBE工具导入大鼠受精卵，然后移植到假孕大鼠中（见下图）。

Qi, X., Chen, X., Guo, J. et al. Precision modeling of mitochondrial disease in rats via DdCBE-mediated mtDNA editing. Cell Discov 7, 95 (2021).

痴呆症

神经系统疾病

1. von Bartheld C S , J ohnson J E. Ta rget-derived BDNF ( brain-derived neurotrophic f actor ) is essential for the survival of developing neurons in the isthmo-optic nucleus [ J ] . J Comp Neurol ,2001 ,433 :550 - 564. 2. Balkowiec A , Katz D M. Activity-dependent release of endogenous brain-derived neurotrophic f actor from primary sensory neurons detected by EL ISA in situ [ J ] . J Neurosci ,2000 ,20 :7417 - 7423. 3. Murer M G , Yan Q , Raisman V R. Brain-derived neurotrophic factor in the control human brain , and in Alzheimer’s disease and Parkinson’s disease[J ] . Prog Neurobiol ,2001 ,63 :71 - 124. 4. Roux P P , Ba rker P A. Neurotrophin signaling through the p75 neurotrophin receptor [J ] . Prog Neurobiol ,2002 ,67 :203 - 233. 5. Patapoutian A , Reichardt L F. Trk receptors : mediators of neurotrophin action[J ] . Curr Opin Neurobiol ,2001 ,11 :272 - 280.

神经系统疾病

小鼠是用全身启动子驱动BDNF siRNA过表达建立的全身过表达BDNF siRNA小鼠，抑制BDNF的表达。

1. von Bartheld C S , J ohnson J E. Ta rget-derived BDNF ( brain-derived neurotrophic f actor ) is essential for the survival of developing neurons in the isthmo-optic nucleus [ J ] . J Comp Neurol ,2001 ,433 :550 - 564. 2. Balkowiec A , Katz D M. Activity-dependent release of endogenous brain-derived neurotrophic f actor from primary sensory neurons detected by EL ISA in situ [ J ] . J Neurosci ,2000 ,20 :7417 - 7423. 3. Murer M G , Yan Q , Raisman V R. Brain-derived neurotrophic factor in the control human brain , and in Alzheimer’s disease and Parkinson’s disease[J ] . Prog Neurobiol ,2001 ,63 :71 - 124. 4. Roux P P , Ba rker P A. Neurotrophin signaling through the p75 neurotrophin receptor [J ] . Prog Neurobiol ,2002 ,67 :203 - 233. 5. Patapoutian A , Reichardt L F. Trk receptors : mediators of neurotrophin action[J ] . Curr Opin Neurobiol ,2001 ,11 :272 - 280.