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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Transgenes

  • Infusion of recombinant adenoviruses containing the VLDL receptor gene corrected the dsylipidaemia in the FH mouse and circumvented immune responses to the transgene leading to a more prolonged metabolic correction [1].
  • Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle [2].
  • Crossing a human transgene encoding p75NGFR into the mutant animals rescued the absent heat sensitivity and the occurrence of skin ulcers and increased the density of neuropeptide-immunoreactive sensory innervation of footpad skin [3].
  • The epithelial hyperplastic phenotype caused by the LMP-encoding transgenes implies that the LMP plays a role in the acanthotic condition of the tongue epithelium in the human EBV- and HIV-associated syndrome oral hairy leukoplakia, as well as possibly predisposing the nasopharyngeal epithelium to carcinogenesis [4].
  • Remarkably, no humoral or cellular immune responses are elicited to the neoantigenic transgene product E. coli beta-galactosidase [5].

Psychiatry related information on Transgenes

  • The perception of odors or electroshock remained normal when the lio+ transgene was expressed in these lio1 flies [6].
  • Conditional mouse models of polyglutamine diseases, such as Huntington's disease (HD), have revealed that cells can clear accumulated pathogenic proteins if the continuous production of the mutant transgene is halted [7].
  • The sporadic nature of the tumors, the long latency period prior to their development, and low levels of transgene expression in the tumors indicate that PTPepsilon provides a necessary, but insufficient, signal for oncogenesis [8].
  • Together, these results suggest that the high permissiveness of RPE cells is not related to the presence of heparan sulfate receptors or nuclear trafficking but may be due to an enhanced rate of second-strand synthesis and that integration in RPE cells is responsible for long-term transgene expression [9].
  • In addition, spatial learning was impaired in transgenic mice expressing transgenes for NFH and NFM, similar to the memory deficits reported in patients with ALS [10].

High impact information on Transgenes

  • Our results contradict both models and show instead that transcriptional silencing at several URA3 transgenes, and at the naturally silenced endogenous HMRa and HMLalpha mating type genes, acts downstream of gene activator protein binding to strongly reduce the occupancy of TFIIB, RNA polymerase II, and TFIIE at the silenced promoters [11].
  • MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression [12].
  • Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence [13].
  • Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion [14].
  • Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels [15].

Chemical compound and disease context of Transgenes


Biological context of Transgenes

  • A 140 kb BAC transgene completely rescued both the long period and the loss-of-rhythm phenotypes in Clock mutant mice [21].
  • However, enhancer mutations that result in increased rates of transgene silencing fail to localize the transgene away from centromeric heterochromatin, even when the transgene is in an active state [22].
  • We placed this element on a removable cassette adjacent to a human HBB (encoding beta-globin) reporter and generated a transgene whose methylation pattern can be switched in vivo [23].
  • Thus, when male mice carrying a Y-linked transgene containing inverted loxP sites are mated with females carrying a cre gene that is obiquitously expressed in the early embryo, almost all their XY progeny lose the Y chromosome early in embryogenesis and develop as XO females [24].
  • The dominant interference of the Hox-1.1 transgene with developmental programs seems to occur around day 9 of gestation, the time of neural crest migration and somite differentiation [25].

Anatomical context of Transgenes

  • Here, we show that enforced expression of the bcl-2 gene in T-lymphoid cells (by crossing in the Emu-bcl-2 transgene) in IL-7R alpha-deficient mice results in a significant restoration of thymic positive selection and T cell numbers and function [26].
  • Here we show that expression of a truncated utrophin transgene solely within the skeletal muscle of these mutants prevents premature death and the development of any clinical phenotype [27].
  • We recently showed that Gata3-directed lacZ expression of a 625-kb Gata3 YAC transgene in mice mimics endogenous Gata3 expression, except in thymus and the sympathoadrenal system [28].
  • The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice [29].
  • Mld and shiverer mice with zero, one, or two copies of the MBP transgene express distinct levels of MBP mRNA and myelin [30].

Associations of Transgenes with chemical compounds

  • To test whether the hypothesis that the Alzheimer's A beta peptide is neurotoxic, we introduced a transgene into mice to direct expression of this peptide to neurons [31].
  • Using a loxP-flanked Tfam allele (TfamloxP) in combination with a cre-recombinase transgene under control of the muscle creatinine kinase promoter, we have disrupted Tfam in heart and muscle [32].
  • LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone [33].
  • Superweed study falters as seed firms deny access to transgene [34].
  • To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression [35].

Gene context of Transgenes

  • Postnatally, Xist is expressed only from the transgene [36].
  • Inhibiting BRCA1 synthesis in a suitable reporter line led to increased expression of an otherwise silenced Xi-located GFP transgene [37].
  • These changes are blocked by coexpression of a TIMP1 transgene [38].
  • Overexpression of the Clock transgene can shorten period length beyond the wild-type range, which provides additional evidence that Clock is an integral component of the circadian pacemaking system [21].
  • Here, we report that a cosmid transgene overexpressing Pla2g2a caused a reduction in tumour multiplicity and size, comparable to that conferred by a single copy of the resistance allele of Mom1 [39].

Analytical, diagnostic and therapeutic context of Transgenes


  1. Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Kozarsky, K.F., Jooss, K., Donahee, M., Strauss, J.F., Wilson, J.M. Nat. Genet. (1996) [Pubmed]
  2. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Musarò, A., McCullagh, K., Paul, A., Houghton, L., Dobrowolny, G., Molinaro, M., Barton, E.R., Sweeney, H.L., Rosenthal, N. Nat. Genet. (2001) [Pubmed]
  3. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Lee, K.F., Li, E., Huber, L.J., Landis, S.C., Sharpe, A.H., Chao, M.V., Jaenisch, R. Cell (1992) [Pubmed]
  4. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Wilson, J.B., Weinberg, W., Johnson, R., Yuspa, S., Levine, A.J. Cell (1990) [Pubmed]
  5. Recombinant adeno-associated virus for muscle directed gene therapy. Fisher, K.J., Jooss, K., Alston, J., Yang, Y., Haecker, S.E., High, K., Pathak, R., Raper, S.E., Wilson, J.M. Nat. Med. (1997) [Pubmed]
  6. Molecular cloning of linotte in Drosophila: a novel gene that functions in adults during associative learning. Bolwig, G.M., Del Vecchio, M., Hannon, G., Tully, T. Neuron (1995) [Pubmed]
  7. Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. Yamamoto, A., Cremona, M.L., Rothman, J.E. J. Cell Biol. (2006) [Pubmed]
  8. Protein tyrosine phosphatase epsilon increases the risk of mammary hyperplasia and mammary tumors in transgenic mice. Elson, A. Oncogene (1999) [Pubmed]
  9. Kinetics of efficient recombinant adeno-associated virus transduction in retinal pigment epithelial cells. Lai, Y.K., Rolling, F., Baker, E., Rakoczy, P.E. Exp. Cell Res. (2001) [Pubmed]
  10. Neurobehavioral characteristics of mice with modified intermediate filament genes. Lalonde, R., Strazielle, C. Reviews in the neurosciences. (2003) [Pubmed]
  11. Mechanism of transcriptional silencing in yeast. Chen, L., Widom, J. Cell (2005) [Pubmed]
  12. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Mansfield, J.H., Harfe, B.D., Nissen, R., Obenauer, J., Srineel, J., Chaudhuri, A., Farzan-Kashani, R., Zuker, M., Pasquinelli, A.E., Ruvkun, G., Sharp, P.A., Tabin, C.J., McManus, M.T. Nat. Genet. (2004) [Pubmed]
  13. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Pollock, P.M., Cohen-Solal, K., Sood, R., Namkoong, J., Martino, J.J., Koganti, A., Zhu, H., Robbins, C., Makalowska, I., Shin, S.S., Marin, Y., Roberts, K.G., Yudt, L.M., Chen, A., Cheng, J., Incao, A., Pinkett, H.W., Graham, C.L., Dunn, K., Crespo-Carbone, S.M., Mackason, K.R., Ryan, K.B., Sinsimer, D., Goydos, J., Reuhl, K.R., Eckhaus, M., Meltzer, P.S., Pavan, W.J., Trent, J.M., Chen, S. Nat. Genet. (2003) [Pubmed]
  14. Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Tanner, S.M., Aminoff, M., Wright, F.A., Liyanarachchi, S., Kuronen, M., Saarinen, A., Massika, O., Mandel, H., Broch, H., de la Chapelle, A. Nat. Genet. (2003) [Pubmed]
  15. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., Smith, A. Cell (2003) [Pubmed]
  16. Autoimmune diabetes can be induced in transgenic major histocompatibility complex class II-deficient mice. Laufer, T.M., von Herrath, M.G., Grusby, M.J., Oldstone, M.B., Glimcher, L.H. J. Exp. Med. (1993) [Pubmed]
  17. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. Temann, U.A., Ray, P., Flavell, R.A. J. Clin. Invest. (2002) [Pubmed]
  18. Tumor-specific gene delivery using recombinant vaccinia virus in a rabbit model of liver metastases. Gnant, M.F., Noll, L.A., Irvine, K.R., Puhlmann, M., Terrill, R.E., Alexander, H.R., Bartlett, D.L. J. Natl. Cancer Inst. (1999) [Pubmed]
  19. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. Marber, M.S., Mestril, R., Chi, S.H., Sayen, M.R., Yellon, D.M., Dillmann, W.H. J. Clin. Invest. (1995) [Pubmed]
  20. Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. Waxman, A.B., Einarsson, O., Seres, T., Knickelbein, R.G., Warshaw, J.B., Johnston, R., Homer, R.J., Elias, J.A. J. Clin. Invest. (1998) [Pubmed]
  21. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Antoch, M.P., Song, E.J., Chang, A.M., Vitaterna, M.H., Zhao, Y., Wilsbacher, L.D., Sangoram, A.M., King, D.P., Pinto, L.H., Takahashi, J.S. Cell (1997) [Pubmed]
  22. A functional enhancer suppresses silencing of a transgene and prevents its localization close to centrometric heterochromatin. Francastel, C., Walters, M.C., Groudine, M., Martin, D.I. Cell (1999) [Pubmed]
  23. DNA methylation represses transcription in vivo. Siegfried, Z., Eden, S., Mendelsohn, M., Feng, X., Tsuberi, B.Z., Cedar, H. Nat. Genet. (1999) [Pubmed]
  24. Cre-mediated chromosome loss in mice. Lewandoski, M., Martin, G.R. Nat. Genet. (1997) [Pubmed]
  25. Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice. Kessel, M., Balling, R., Gruss, P. Cell (1990) [Pubmed]
  26. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Akashi, K., Kondo, M., von Freeden-Jeffry, U., Murray, R., Weissman, I.L. Cell (1997) [Pubmed]
  27. Skeletal muscle-specific expression of a utrophin transgene rescues utrophin-dystrophin deficient mice. Rafael, J.A., Tinsley, J.M., Potter, A.C., Deconinck, A.E., Davies, K.E. Nat. Genet. (1998) [Pubmed]
  28. Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Lim, K.C., Lakshmanan, G., Crawford, S.E., Gu, Y., Grosveld, F., Engel, J.D. Nat. Genet. (2000) [Pubmed]
  29. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Jansen, G., Groenen, P.J., Bächner, D., Jap, P.H., Coerwinkel, M., Oerlemans, F., van den Broek, W., Gohlsch, B., Pette, D., Plomp, J.J., Molenaar, P.C., Nederhoff, M.G., van Echteld, C.J., Dekker, M., Berns, A., Hameister, H., Wieringa, B. Nat. Genet. (1996) [Pubmed]
  30. Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin. Popko, B., Puckett, C., Lai, E., Shine, H.D., Readhead, C., Takahashi, N., Hunt, S.W., Sidman, R.L., Hood, L. Cell (1987) [Pubmed]
  31. The Alzheimer's A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice. LaFerla, F.M., Tinkle, B.T., Bieberich, C.J., Haudenschild, C.C., Jay, G. Nat. Genet. (1995) [Pubmed]
  32. Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Wang, J., Wilhelmsson, H., Graff, C., Li, H., Oldfors, A., Rustin, P., Brüning, J.C., Kahn, C.R., Clayton, D.A., Barsh, G.S., Thorén, P., Larsson, N.G. Nat. Genet. (1999) [Pubmed]
  33. Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene. Lozano, F., Rada, C., Jarvis, J.M., Milstein, C. Nature (1993) [Pubmed]
  34. Superweed study falters as seed firms deny access to transgene. Dalton, R., Diego, S. Nature (2002) [Pubmed]
  35. Control of memory formation through regulated expression of a CaMKII transgene. Mayford, M., Bach, M.E., Huang, Y.Y., Wang, L., Hawkins, R.D., Kandel, E.R. Science (1996) [Pubmed]
  36. A 450 kb transgene displays properties of the mammalian X-inactivation center. Lee, J.T., Strauss, W.M., Dausman, J.A., Jaenisch, R. Cell (1996) [Pubmed]
  37. BRCA1 supports XIST RNA concentration on the inactive X chromosome. Ganesan, S., Silver, D.P., Greenberg, R.A., Avni, D., Drapkin, R., Miron, A., Mok, S.C., Randrianarison, V., Brodie, S., Salstrom, J., Rasmussen, T.P., Klimke, A., Marrese, C., Marahrens, Y., Deng, C.X., Feunteun, J., Livingston, D.M. Cell (2002) [Pubmed]
  38. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Sternlicht, M.D., Lochter, A., Sympson, C.J., Huey, B., Rougier, J.P., Gray, J.W., Pinkel, D., Bissell, M.J., Werb, Z. Cell (1999) [Pubmed]
  39. Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Cormier, R.T., Hong, K.H., Halberg, R.B., Hawkins, T.L., Richardson, P., Mulherkar, R., Dove, W.F., Lander, E.S. Nat. Genet. (1997) [Pubmed]
  40. A counterdefensive strategy of plant viruses: suppression of posttranscriptional gene silencing. Kasschau, K.D., Carrington, J.C. Cell (1998) [Pubmed]
  41. Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. Cox, G.A., Cole, N.M., Matsumura, K., Phelps, S.F., Hauschka, S.D., Campbell, K.P., Faulkner, J.A., Chamberlain, J.S. Nature (1993) [Pubmed]
  42. Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Miyoshi, H., Smith, K.A., Mosier, D.E., Verma, I.M., Torbett, B.E. Science (1999) [Pubmed]
  43. Genetic regulation of glutamate receptor ion channels. Myers, S.J., Dingledine, R., Borges, K. Annu. Rev. Pharmacol. Toxicol. (1999) [Pubmed]
  44. legless insertional mutation: morphological, molecular, and genetic characterization. Singh, G., Supp, D.M., Schreiner, C., McNeish, J., Merker, H.J., Copeland, N.G., Jenkins, N.A., Potter, S.S., Scott, W. Genes Dev. (1991) [Pubmed]
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