Crebbp Conditional Knockout mouse models

CREB binding protein, encoded by Crebbp and orthologous to human CREBBP, is a KAT3 family lysine acetyltransferase that deposits H3K18 and H3K27 acetylation at enhancers and, through KIX, TAZ1, TAZ2, bromodomain, and nuclear coactivator binding modules, bridges sequence-specific factors including CREB, TP53, MYB, and IRF proteins to the basal machinery. Lymphoma alleles are dominated by HAT domain missense substitutions such as R1446C and by truncations that reduce enhancer acetylation at MHC class II and BCL6 target loci, while germline heterozygous loss produces Rubinstein-Taybi syndrome. Homozygous deletion is embryonic lethal with hematopoietic and neural tube defects, making conditional deletion the practical route, and catalytically dead knockins separate acetyltransferase output from scaffolding. The paralog Ep300 shares substrates and buffers partial loss, which is exactly why CREBBP mutant tumors show heightened EP300 dependency. Use heterozygous conditional loss for immune evasion endpoints and compound Crebbp with Ep300 alleles for synthetic lethality validation.

Conditional deletion of Crebbp limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Crebbp floxed stock yields usable cohorts.