Mga, also known as Max gene associated, is a dual-specificity transcription factor. It negatively regulates MYC-target genes, thus inhibiting proliferation and promoting differentiation [6]. It is involved in multiple biological processes, such as embryogenesis, where it regulates the expression of Max-network and T-box family target genes [5]. It is also part of the Polycomb group (PcG) proteins, which affect stem cell identity and fate decisions [3].

In leukemia research, knockout of Mga in the Sf3b1/Mdr CLL model established an RT mouse model. Murine RT cells showed mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS), and Nme1 was identified as an Mga target that drives Richter's transformation (RT) by modulating OXPHOS. Concurrent inhibition of MYC and electron transport chain complex II prolonged the survival of RT mice in vivo, suggesting the Mga-Nme1 axis drives CLL-to-RT transition via modulating OXPHOS [1,4]. In acute myeloid leukemia with RUNX1::RUNX1T1, loss of MGA in murine hematopoietic cells led to upregulation of MYC and E2F targets, cell cycle genes, mTOR signaling, and oxidative phosphorylation, enhancing proliferation and resulting in a more aggressive AML with shortened latency [6].

In female reproduction, Mga+/- female mice were subfertile, mimicking the phenotype of human patients with MGA loss-of-function variants, highlighting the essential role of MGA in female reproductive ability [2].

In conclusion, Mga plays a crucial role in multiple biological processes. Gene knockout mouse models have been instrumental in revealing its role in diseases such as leukemia and premature ovarian insufficiency. These models provide valuable insights into the molecular mechanisms underlying these diseases, potentially paving the way for new therapeutic strategies.