Bcl6 Conditional Knockout mouse models

B cell lymphoma 6, encoded by Bcl6 and orthologous to human BCL6, is a BTB/POZ zinc finger transcriptional repressor whose homodimer lateral groove recruits NCOR, SMRT, and BCOR corepressors while its RD2 region engages MTA3 and NuRD. As master regulator of the germinal center reaction it silences Trp53, Cdkn1a, Atr, and Prdm1, permitting tolerated DNA damage during somatic hypermutation and blocking plasma cell differentiation. Lymphoma activation arises from IGH or promoter substitution translocations and 5-prime regulatory mutations that prevent normal downregulation, yielding constitutive expression in diffuse large B cell lymphoma. Design accordingly: conditional deletion defines germinal center dependency, a knockin or promoter substitution allele driving sustained expression models lymphomagenesis, and BTB groove point mutants separate corepressor-dependent from independent functions for degrader and inhibitor programs. Germline nulls are viable but develop inflammatory myocarditis, so Cd19-Cre or Cgamma1-Cre restriction keeps phenotypes interpretable against B cell endpoints.

Tissue restricted knockout of Bcl6 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.