@article{TEXTUAL,
      recid = {10480},
      author = {Gong, Jianhua and Wang, Zhongde and Polejaeva, Irina and  Salgia, Ravi and Kao, Chien-Min and Chen, Chin-Tu and Chen,  Guangchun and Chen, Liaohai},
      title = {Activating the Expression of Human  K-ras<sup>G12D</sup> Stimulates Oncogenic  Transformation in Transgenic Goat Fetal Fibroblast Cells},
      journal = {PLOS ONE},
      address = {2014-03-04},
      number = {TEXTUAL},
      abstract = {<p>Humane use of preclinical large animal cancer models  plays a critical role in understanding cancer biology and  developing therapeutic treatments. Among the large animal  candidates, goats have great potentials as sustainable  sources for large animal cancer model development. Goats  are easier to handle and cheaper to raise. The genome of  the goats has been sequenced recently. It has been known  that goats develop skin, adrenal cortex, breast and other  types of cancers. Technically, goats are subject to somatic  cell nuclear transfer more efficiently and exhibit better  viability through the cloning process. Towards the  development of a goat cancer model, we created a transgenic  goat fetal fibroblast (GFF) cell as the donor cell for  SCNT. Human mutated K-ras (hK-ras<sup>G12D</sup>) was  chosen as the transgene, as it is present in 20% of  cancers. Both hK-ras<sup>G12D</sup> and a herpes simplex  viral thymidine kinase (HSV1-tk) reporter genes, flanked by  a pair of LoxP sites, were knocked in the GFF endogenous  K-ras locus through homologous recombination. Following  Cre-mediated activation (with a 95% activation efficiency),  hK-ras<sup>G12D</sup> and HSV1-tk were expressed in the  transgenic GFF cells, evidently through the presence of  corresponding mRNAs, and confirmed by HSV1-tk protein  function assay. The hK-ras<sup>G12D</sup> expressing GFF  cells exhibited enhanced proliferation rates and an  anchorage-independent growth behavior. They were able to  initiate tumor growth in athymic nude mice. In conclusion,  after activating hK-ras<sup>G12D</sup> gene expression,  hK-ras<sup>G12D</sup> transgenic GFF cells were transformed  into tumorgenesis cells. Transgenic goats via SCNT using  the above-motioned cells as the donor cells have been  established.</p>},
      url = {http://knowledge.uchicago.edu/record/10480},
}