痴呆症；帕金森病

基因打靶

1. Michetti F，Cazzlo D. S100B protein in biological fluids：a tool for perinatal medicine. Clin Chem. 2002；48（12）：2097 2. Hauschild A，Engel G，Brenner W，et al . S100B protein detection in serum is a significant prognostic factor in metastatic melanoma. Oncology. 1999；56（4）：338 3. Rustandi RR， Baldisseri DM， Weber DJ. Structure of the negative regulatory domain of p53 bound to S100B（betabeta）. Nat Struct Bio1. 2000；7（7）：570

痴呆症；帕金森病

1Crameri A, Biondi E, Kuehnle K, et al. The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. EMBO J. 2006, 25(2):432-43. 2 Wechsler A, Brafman A, Shafir M, et al. Generation of viable cholesterol-free mice. Science 2003, 302: 2087. 3 Greeve I, Hermans-Borgmeyer I, Brellinger C, et al. The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress. J. Neurosci. 2000, 20: 7345-7352. 4 Kuehnle K, Crameri A, Kalin RE, et al. Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Mol Cell Biol. 2008, 28(2): 539-50.

代谢系统疾病；糖尿病；肥胖症

转基因小鼠

1 杜静，秦川．胆囊收缩素作用的研究进展．中国比较医学杂志．2007，17（4）： 67-75． 2 Liddle RA. Cholecystokinin: its role in health and disease Curr Opin Endocrinol. Diabetes, 2003, 10(1):50-54. 3 Blevins JE, Stanley BG, Reidelberger RD. Brain regions where cholecystokinin suppresses feeding in rats. Brain Res, 2000, 860:1-10. 4 Appleyard SM, Bailey TW,Doyle MW,et al. Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids. Neuroscience, 2005, 25(14):3578-3585.

神经系统疾病；发育障碍疾病相关模型

胚胎干细胞打靶

1 Artavanis-Tsakonas S，Matsuono K，Fortini M. Notch signaling. Science 268: 225-232, 1995. 2 Axelrod JD, Matsuno K, Artavanis-Tsakonas S, et al . Interaction between Wingless and Notch signaling pathways mediated by Dishevelled. Science 271: 1826-1832, 1996. 3. Fre S, Huyghe M, Mourikis P,et al. Notch signals control the fate of immature progenitor cells in the intestine. (Letter) Nature 435: 964-968, 2005. 4 Garg V, Muth AN, Ransom JF, et al. Mutations in NOTCH1 cause aortic valve disease. Nature 437: 270-274, 2005.

神经系统相关疾病

胚胎干细胞打靶

1 Kamei Y, Tsutsumi O, Taketani Y, et al. cDNA cloning and chromosomal localization of neural adhesion molecule NB-3 in human. J. Neurosci. Res. 51: 275-283, 1998. 2 Lee S, Takeda Y, Kawano H, et al.Expression and regulation of a gene encoding neural recognition molecule NB-3 of the contactin/F3 subgroup in mouse brain. Gene 245: 253-266, 2000.

荧光工具小鼠

Egr-1启动EGFP转基因

3P综合征；白血病

基因打靶

1. Angeloni, D.; Lindor, N. M.; Pack, S.,et al., CALL gene is haploinsufficient in a 3p- syndrome patient. Am. J. Med. Genet. 86: 482-485, 1999. 2. Frints, S. G. M.; Marynen, P.; Hartmann, D.,et al., CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior. Hum. Molec. Genet. 12: 1463-1474, 2003. 3. Kozma, C.; Slavotinek, A. M.; Meck, J. M. : Segregation of a t(1;3) translocation in multiple affected family members with both types of adjacent-1 segregants. Am. J. Med. Genet. 124A: 118-128, 2004. 4. Wei, M.-H.; Karavanova, I.; Ivanov, S. V.et al., In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules. Hum. Genet. 103: 355-364, 1998.

代谢系统疾病；糖尿病；肥胖症

基因打靶

1 杜静，秦川．胆囊收缩素作用的研究进展．中国比较医学杂志．2007，17（4）： 67-75． 2 Liddle RA. Cholecystokinin: its role in health and disease Curr Opin Endocrinol. Diabetes, 2003, 10(1):50-54. 3 Blevins JE, Stanley BG, Reidelberger RD. Brain regions where cholecystokinin suppresses feeding in rats. Brain Res, 2000, 860:1-10. 4 Appleyard SM, Bailey TW,Doyle MW,et al. Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids. Neuroscience, 2005, 25(14):3578-3585.

免疫相关疾病

FRI-ZZ-LE9 - B2M/ FRI-ZZ-LE9 – H2K 将FRI-ZZ-LE9启动子和B2M靶基因构建的载体与FRI-ZZ-LE9启动子和H2K靶基因构建的载体同时注射到小鼠的受精卵。

1. Huh, G. S.; Boulanger, L. M.; Du, H.; Functional requirement for class I MHC in CNS development and plasticity. Science 290: 2155-2159, 2000. 2. Wani, M. A.; Haynes, L. D.; Kim, J.; et al.Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta-2-microglobulin gene. Proc. Nat. Acad. Sci. 103: 5084-5089, 2006.

痴呆症相关模型

胚胎干细胞打靶

1 Calhoun ME, Wiederhold K-H, Abramowski, et al. Neuron loss in APP transgenic mice. Nature 395: 755-756, 1998. 2 Cao X, Sudhof TC, A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293: 115-120, 2001. 3 Carter DA, Desmarais E, Bellis,et al. More missense in amyloid gene. (Letter) Nature Genet. 2: 255-256, 1992. 4 Chen AC, Selkoe DJ. Response, et al., 'Presenilin-dependent transcriptional control of the A-beta-degrading enzyme neprilysin by intracellular domains of beta-APP and APLP. Neuron 46, 541-554. Neuron 53: 479-483, 2007. 5 Cheng IH, Palop JJ, Esposito, et al. Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nature Med. 10: 1190-1192, 2004. 6 Colton CA, Vitek MP, Wink D, et al. NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease. Proc. Nat. Acad. Sci. 103: 12867-12872, 2006. Note: Erratum: Proc. Nat. Acad. Sci 103: 15273 only, 2006. l 7 Khoury J, Toft M,Hickman SE, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Med. 13: 432-438, 2007.

乳腺癌

条件性敲除

免疫相关疾病

转基因小鼠