Fig. 3

The figure illustrates different types of genetically engineered mouse models (GEMMs) for studying PI3K-driven breast cancer. The color scheme represents different genetic alterations in the mouse tissues. Wildtype tissues are depicted in white, knockout tissues are shown in gray, and tissues expressing a transgene or knock-in gene are represented in blue. A Conventional knockout mice exhibit inactivation of tumor suppressor genes (TSGs) in all tissues. B Conditional knockout models can be created by flanking critical exons of TSGs with loxP sequences. This allows tissue-specific inactivation of the TSG through Cre site-specific recombinase action, achieved by utilizing a tissue-specific promoter to control Cre expression. C Hypomorphic mouse models can be generated by inserting a neomycin cassette into intronic regions, leading to transcriptional interference and reduced expression of the targeted TSG. D Constitutive transgenic models involve the insertion of a transgene into the host genome under the control of a tissue-specific promoter (TSP), enabling tissue-specific expression of the gene of interest (GOI). E Conditional transgenic systems utilize loxP sites to flank a transcriptional termination sequence (represented by a STOP sign). Recombination by Cre recombinase removes the STOP sequence, allowing tissue-specific expression of the GOI. F Doxycycline-inducible 'tet-on' systems rely on the tissue-specific expression of a transactivator (rtTA) that binds to the Tet operator (TetO) and activates expression of the GOI only in the presence of doxycycline (dox). These various GEMMs provide valuable tools to study the role of PI3K signaling in breast cancer by enabling the investigation of tissue-specific effects and the regulation of gene expression