Fig. 1

DNMT3A and DNMT3B isoforms in mouse. Conserved regions are colored, and their respective functions are indicated below. The conserved domain IV in the catalytic region of Dnmt3a is flanked by the loxP sites is indicated in red. HSJS stands for Heyn-Sproul-Jackson syndrome, associated with mutations in the DNMT3A PWWP domain. The W326R mutation is homologous to the human W330R disease-causing mutation and recapitulates the disease phenotype (see under “Medical Relevance” chapter). TBRS represents Tattoon-Brown Rahman Syndrome, AML indicates acute myeloid leukemia. Both can develop due to the dominant R382H mutation in human. The corresponding mouse mutation R878H is indicated. DNMT3B isoforms are shown on the panel below. The conserved domains I - VI in the catalytic region of Dnmt3b flanked by the loxP sites are indicated in red. A609T and D823G mutations cause similar phenotype than the human ICF syndrome (immunodeciency-centromeric instability-facial dismorphism). Homologous A603T and D817G mutations were reported in ICF patients