Kmt2d Conditional Knockout mouse models

Among enhancer regulators, Kmt2d is the mouse ortholog of human KMT2D (MLL2 or MLL4) and the dominant H3K4 monomethyltransferase of the COMPASS-like complex, working through NCOA6, PTIP, PA1, RBBP5, ASH2L, and UTX to prime enhancers that drive B cell, cardiac, and neural differentiation programs. Heterozygous truncating variants cause Kabuki syndrome, while somatic nonsense and frameshift mutations dominate follicular lymphoma, diffuse large B cell lymphoma, bladder carcinoma, and lung squamous cancer, implicating enhancer collapse and impaired germinal center exit rather than gain of function. Because germline nulls die in midgestation with cardiac and neural tube defects, conditional nulls remain the practical route for lineage-restricted enhancer studies, whereas SET-dead knockins separate catalysis from scaffolding and humanized alleles support classification of clinical missense variants. The paralog Kmt2c shares substrate and complex membership, so masked phenotypes are a genuine risk; align allele class with endpoint and use germinal center drivers such as Cgamma1-cre for lymphomagenesis.

Kmt2d 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.