重组酶工具小鼠

转基因小鼠

免疫疾病相关疾病小鼠

干细胞打靶

肿瘤疾病相关模型小鼠

干细胞打靶

1 Adams RH, Porras A, Alonso. Essential role of p38-alpha MAP kinase in placental but not embryonic cardiovascular development. Molec. Cell 6: 109-116, 2000. 2 Agrawal A, Lingappa J. Leppla Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 424: 329-334, 2003. 3 Anhalt GJ, Labib RS. Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease. New Eng. J. Med. 306: 1189-1196, 1982. 4 Berkowitz P, Hu P, Warren S. p38MAPK inhibition prevents disease in pemphigus vulgaris mice. Proc. Nat. Acad. Sci. 103: 12855-12860, 2006.

肿瘤疾病相关模型小鼠

自发突变

肿瘤疾病相关模型小鼠

转基因小鼠

细胞凋亡相关模型小鼠

基因敲除

1 Chang L, Jones Y, Ellisman MH, et al. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell 4: 521-533, 2003. 2 Chang NS, Doherty J, Ensign A.JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J. Biol. Chem. 278: 9195-9202, 2003. 3 Derijard B, Hibi M, Wu IH,et al.JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025-1037, 1994. 4 De Smaele E, Zazzeroni F, Papa S, et al.Induction of gadd45-beta by NF-kappa-B downregulates pro-apoptotic JNK signaling. Nature 414: 308-313, 2001. 5 Dong C, Yang DD, Tournier C,et al. JNK is required for effector T-cell function but not for T-cell activation. Nature 405: 91-94, 2000 6 Fuchs SY, Adler V, Buschmann T, et al.JNK targets p53 ubiquitination and degradation in nonstressed cells. Genes Dev. 12: 2658-2663, 1998. 7 Han Z, Chang L, Yamanishi Y, et al.Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritis. Arthritis Rheum. 46: 818-823, 2002.

糖尿病疾病相关模型小鼠

基因敲除

1 Chang L, Jones Y, Ellisman MH, et al. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell 4: 521-533, 2003. 2 Chang NS, Doherty J, Ensign A.JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J. Biol. Chem. 278: 9195-9202, 2003. 3 Derijard B, Hibi M, Wu IH,et al.JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025-1037, 1994. 4 De Smaele E, Zazzeroni F, Papa S, et al.Induction of gadd45-beta by NF-kappa-B downregulates pro-apoptotic JNK signaling. Nature 414: 308-313, 2001. 5 Dong C, Yang DD, Tournier C,et al. JNK is required for effector T-cell function but not for T-cell activation. Nature 405: 91-94, 2000 6 Fuchs SY, Adler V, Buschmann T, et al.JNK targets p53 ubiquitination and degradation in nonstressed cells. Genes Dev. 12: 2658-2663, 1998. 7 Han Z, Chang L, Yamanishi Y, et al.Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritis. Arthritis Rheum. 46: 818-823, 2002.

糖尿病疾病相关模型小鼠

基因敲除

1 Chang L, Jones Y, Ellisman MH, et al. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell 4: 521-533, 2003. 2 Chang NS, Doherty J, Ensign A.JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J. Biol. Chem. 278: 9195-9202, 2003. 3 Derijard B, Hibi M, Wu IH,et al.JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025-1037, 1994.

免疫疾病相关模型小鼠

基因敲除

1 Miscia S, Marchisio M,Grilli A, et al.Tumornecrosis factor alpha (TNF-α activatesJak1/Stat3-Stat5B signaling through TNFR-1 in human B cells. Cell Growth Differ, 2002, 13(1):13-18. 2 Riley JK,Takeda K,Akira S, et al.Interleukin-10receptor signaling through the JAK-STAT pathway.J Biol Chem,1999,274(23):16513-16521.

肿瘤疾病相关模型小鼠

胚胎干细胞打靶，通过同源重组，Gadd45a基因的3.65kb片段（包括上游序列和外显子1-3）被PGK-neo盒取代。

1. Barreto, G., Schafer, A. Marhold, J., Stach, D., Swaminathan, S. K., Handa, V., Doderlein, G., Maltry, N., Wu, W., Lyko, F., Niehrs, C. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature vol. 445, 671-675, 2007. [PubMed: 17268471] 2. Bruemmer, D., Yin, F., Liu, J., Berger, J. P., Sakai, T., Blaschke, F., Fleck, E., Van Herle, A. J., Forman, B. M., Law, R. E. Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells. Circ. Res. vol. 93, e38-e47, 2003. [PubMed: 12881480] 3. Carrier, F., Smith, M. L., Bae, I., Kilpatrick, K. E., Lansing, T. J., Chen, C.-Y., Engelstein, M., Friend, S. H., Henner, W. D., Gilmer, T. M., Kastan, M. B., Fornace, A. J., Jr. Characterization of human Gadd45, a p53-regulated protein. J. Biol. Chem. vol. 269, 32672-32677, 1994. [PubMed: 7798274]

肿瘤疾病相关模型小鼠

基因敲除

1. Bardwell, P. D.; Woo, C. J.; Wei, K.; Li, Z.; Martin, A.; Sack, S. Z.; Parris, T.; Edelmann, W.; Scharff, M. D. : Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice. Nature Immun. 5: 224-229, 2004. 2. Genschel, J.; Bazemore, L. R.; Modrich, P. : Human exonuclease I is required for 5-prime and 3-prime mismatch repair. J. Biol. Chem. 277: 13302-13311, 2002. 3. Lee, B.; Nguyen, L. H.; Barsky, D.; Fernandes, M.; Wilson, D. M., III : Molecular interactions of human Exo1 with DNA. Nucleic Acids Res. 30: 942-949, 2002. 4. Mimitou, E. P.; Symington, L. S.: Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 455: 770-774, 2008. 7. Sharma, S.; Sommers, J. A.; Driscoll, H. C.; Uzdilla, L.; Wilson, T. M.; Brosh, R. M., Jr.: The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. J. Biol. Chem. 278: 23487-23496, 2003. 8. Thompson, E.; Meldrum, C. J.; Crooks, R.; McPhillips, M.; Thomas, L.; Spigelman, A. D.; Scott, R. J. : Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations. Clin. Genet. 65: 215-225, 2004. 10. Wei, K.; Clark, A. B.; Wong, E.; Kane, M. F.; Mazur, D. J.; Parris, T.; Kolas, N. K.; Russell, R.; Hou, H., Jr.; Kneitz, B.; Yang, G.; Kunkel, T. A.; Kolodner, R. D.; Cohen, P. E.; Edelmann, W. : Inactivation of exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Genes Dev. 17: 603-614, 2003.

癌症

在ctnna1基因外显子2的两端插入loxp位点

Vasioukhin V; Bauer C; Degenstein L; Wise B; Fuchs E. 2001. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 104(4):605-17PubMed: 11239416MGI: J:67797