Ep300 Conditional Knockout mouse models

Ep300 encodes p300, the mouse ortholog of human EP300 and the second KAT3 family acetyltransferase, which deposits H3K27 acetylation to mark active enhancers, requires autoacetylation of its activation loop for full catalysis, and uses TAZ1, TAZ2, KIX, and bromodomain modules to nucleate coactivator assemblies with HIF1A, TP53, MYB, and nuclear receptors. Cancer alleles include truncations and HAT domain missense mutations in bladder carcinoma, lymphoma, and colorectal tumors, and the paralog relationship is asymmetric enough that CREBBP mutant tumors become dependent on residual p300, an actionable synthetic lethality now targeted by catalytic and bromodomain inhibitors. Homozygous deletion causes embryonic lethality with cardiac and neural defects, so conditional alleles are mandatory for adult studies, and HAT-dead knockins separate enzymatic from scaffolding contributions. Because Crebbp compensates at many enhancers, single conditional deletion often yields muted transcriptional phenotypes, so plan compound genetics with Cre drivers matched to the tumor lineage.

Ep300 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.