Dnmt3b Conditional Knockout mouse models

Dnmt3b, the mouse ortholog of human DNMT3B, encodes a de novo DNA methyltransferase whose PWWP domain preferentially engages H3K36 trimethylation across gene bodies and whose activity is required for methylation of pericentromeric minor satellite repeats, germline gene promoters, and inactive X chromosome CpG islands. Hypomorphic catalytic domain substitutions cause immunodeficiency, centromeric instability, and facial anomalies syndrome, while overexpression of catalytically active and inactive isoforms accompanies promoter hypermethylation in colorectal and hematologic malignancy. Homozygous deletion is lethal in mid to late gestation with neural tube and growth defects, so conditional alleles are the practical route to adult tissue analysis, and knockin of specific syndromic substitutions models graded catalytic loss rather than absence of protein. Dnmt3a covers overlapping but non-identical targets, and only compound deletion broadly collapses de novo methylation. Match allele class to whether the endpoint is repeat methylation, imprint establishment, or tumor promoter hypermethylation.

Dnmt3b 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.