Proof of this concept was provided using mouse models wherein the locus that codes for Cdk4, one of the important gate-keepers of the mammalian cell cycle machinery, was targeted by genetic recombineering [36], [53].
In mouse models, wherein metastatic mammary carcinomas are induced by the doxycycline induction of Neu overexpression, withdrawal of the Neu oncogene by cessation of doxycycline therapy results in complete regression of the mammary tumours and its associated tumour metastases (Moody et al, 2002).
Direct involvement of IFNγ+CD4+ T cells in TB IRIS development is confirmed by a mouse model, wherein the human disease has been mimicked by adoptively transferring naïve CD4+ T cells into M. avium-infected, T cell-deficient (TCRα−/−) mice [5].
In 1994, a Dutch consortium developed a mouse model wherein the Fmr1 gene was knocked out as a model of Fragile X Syndrome (Fmr1 KO mouse).
In sepsis patients, extracellular ATP release in PMNs was elevated on days 0 1, corroborating our previous work in mouse sepsis models, wherein plasma ATP levels were elevated and contributed to PMN activation [7].
We chose to make use of the RIP1-Tag2 transgenic mouse model [ 18], wherein pancreatic islet carcinogenesis occurs secondary to the expression of the SV-40 large T-antigen (Tag) expression under the Rat Insulin Promoter (RIP).
No nephrotoxicity was found in the low-dose and low-dose cohorts, corresponding to another study done using similar injected mass of radioactivity (MBq) 213Bi-DOTATATE as TAT in nude mice in two different tumor models wherein nephrotoxicity was investigated by 99mTc-DMSA as a kidney marker [35].
Whereas several mouse models have exhibited varying forms of retinal degeneration wherein the photoreceptors are not the initial site of pathology, to the best of our knowledge the Adam9 −/− phenotype is unique and no human disease has been previously linked to such a phenotype.
As aforementioned, drug development has been shifted to an R&D mode, which consists of three steps, that is, (1) in vitro study with cell lines in culture dishes, (2) in vivo study with animals, in most cases using xenograft models wherein human cancer cells are inoculated into immunodeficient mice to allow tumor development, and (3) clinical trials in humans.
Furthermore, using cellular and FAS mouse models, we uncover a prominent role for HSF2 in the developing cortex in response to alcohol, wherein HSF2 is essential for HSF1 activation upon EtOH exposure and drives the formation of EtOH-specific HSF1 HSF2 heterotrimers with a distinctive HSF1 post-translational modification profile.
This contrasted with earlier models wherein the random error was assumed to be constant over time.
