Smarcb1 Conditional Knockout mouse models

Loss of Smarcb1, the mouse ortholog of human SMARCB1 (SNF5, INI1, BAF47), removes a core non-catalytic subunit of the BAF chromatin remodeling complex that stabilizes the ATPase module on nucleosomes and directs residual complexes toward typical enhancers, so its absence redistributes SMARCA4 to super-enhancers and creates a striking dependence on PRC2 and EZH2 activity. Biallelic inactivation, frequently 22q11 deletion plus a truncating hit, defines rhabdoid tumor of kidney, atypical teratoid rhabdoid tumor, epithelioid sarcoma, and renal medullary carcinoma, and germline heterozygosity produces rhabdoid tumor predisposition syndrome, making this one of the most genomically simple pediatric cancers. Homozygous germline deletion is lethal shortly after implantation, whereas conditional nulls yield rhabdoid or lymphoid tumors with very short latency, itself a practical design constraint. No paralog compensates, unlike the SMARCA4 and SMARCA2 pair, so single-locus conditional deletion is interpretable; select inducible Cre timing and lineage to control histology and EZH2 inhibitor endpoints.

Tissue restricted knockout of Smarcb1 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.