Widespread de novo DNA methylation normally occurs during embryonic development but which genes are regulated by this epigenetic process is unknown. Now clues to their identity may come from the two mouse strains described on p. by En Li and colleagues. These mice carry missense mutations in DNA methyltransferase 3B (Dnmt3b). In humans, DNMT3B mutations cause a rare inherited disorder called ICF (for immunodeficiency, centromeric instability and facial anomalies) syndrome. To create an animal model of ICF and to investigate the role of Dnmt3b in mouse development, the researchers generated mice with a null Dnmt3b allele and also mice carrying one of two ICF-like missense mutations. The Dnmt3b null allele caused embryonic lethality, but mice carrying homozygous ICF mutations survived to term and exhibited a phenotype that resembled that of human ICF patients. The researchers conclude that Dnmt3b is essential for mouse embryonic development and propose that ICF missense mutations cause only a partial loss of DNMT3B function.
