Dnmt3a-flox Mouse

Dnmt3a, a de novo DNA methyltransferase, is crucial for DNA methylation, an epigenetic process involved in development, aging, and cancer [1,2,4]. DNA methylation by Dnmt3a at cytosines is essential for genome regulation [2]. It plays a significant role in controlling hematopoietic stem cell fate decisions [1].

In mouse chimeras, inactivation of Dnmt3a (Dnmt3a -/-) led to substantial expansion of Dnmt3a -/- hematopoietic stem cells (HSCs) during chronic mycobacterial infection, indicating that IFNγ signaling induced during chronic infection can drive Dnmt3a -loss -of -function clonal hematopoiesis [3]. In another study, DNMT3AR882H, a common Dnmt3a mutation in angioimmunoblastic T -cell lymphoma (AITL), accelerated the development of Tet2 -/-; RHOAG17V AITL in mice, with single -cell transcriptome analyses revealing enhanced interactions between Tfh and B cells [5]. Also, in a stroke mouse model, increased Dnmt3a protein levels were observed in the brain penumbra, and inhibition of Dnmt3a amplified neutrophil-related inflammation, increased infarct volume, and worsened neurobehavioral function [6].

In conclusion, Dnmt3a is essential for DNA methylation and has a significant impact on processes like hematopoietic stem cell fate determination, clonal hematopoiesis, and responses in diseases such as AITL and acute ischemic stroke. Mouse models, especially those with Dnmt3a inactivation or mutation, have been instrumental in revealing these roles, contributing to our understanding of the underlying mechanisms in these disease areas.