permanently inactivated in each cell of the mouse and ii) conditional where the gene
expression undergoes inducible inactivation directly affective the target.
On the contrary, the gain of function reveals information about overexpression of oncogenes
and its effect in carcinogenesis. Four different knock-in models are used, i) constitutive
random insertion model, knock-in permissive locus model, conditional knock-in model and
reporter knock-in model. In addition to the aforementioned transgenic mouse models, new
models have such as non-germline genetically engineered mouse models and alternative
DNA modification techniques such as transposon based insertion mutagenesis, RNA
interference, engineered nucleases and CRISPR/Cas9 system have emerged in studying the
expression of oncogenes.
Mega BCL-2 protein regulates the mitochondrial apoptotic response, thereby possessing the
ability to suppress apoptosis leading to the development of cancer (Hata et al., 2015).
Furthermore, BH3 mimetic drugs offer a new chemotherapy for cancer by binding to BCL-2
family members and neutralizing the anti-apoptotic effect (Merino et al.,2018). Henceforth,
in this study, a transgenic mouse model will be created with the overexpression of Mega
BCL-2 protein. Additionally, M-BH33, a new BH3 mimetic will be inventedand administered
to evaluate its impact on the expression of Mega BCL-2 protein in the transgenic mouse
model.
Hypothesis
 Overexpression of Mega BCL-2 protein in a transgenic cell could suppress apoptosis
and stimulate carcinogenesis
 The new drug M-BH33 inhibits the anti-apoptotic protein Mega BCL-2 from
proliferation
 The drug leads to overexpression of BH3 pro-apoptotic protein

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Efficacy of M-BH33, the new BH3 mimetic drug on Mega BCL-2

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