Bcl2 Conditional Knockout mouse models

Bcl2 is the mouse ortholog of human BCL2 and encodes the founding antiapoptotic guardian of the mitochondrial pathway, a tail-anchored protein whose BH1, BH2, and BH3 helices form an elongated hydrophobic groove that captures the BH3 helices of activators and effectors, restraining BAX and BAK before permeabilization. Its oncogenic biology is dosage driven rather than mutational: the human t(14;18) translocation places BCL2 under immunoglobulin heavy chain control in follicular lymphoma, best recapitulated in mice by Emu-driven or conditionally activated overexpression rather than a point mutant. Nulls survive birth but develop polycystic kidneys, lymphoid involution, and hair greying. Because Bcl2l1, Mcl1, and Bcl2l2 buffer loss in most tissues, single deletion often looks silent. Epitope-matched humanization is the decisive design when venetoclax pharmacology is the endpoint, including engineered Gly101Val resistance, while conditional nulls and inducible overexpression alleles answer survival dependency and lymphomagenesis questions respectively.

Tissue restricted knockout of Bcl2 keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.