Polb-flox Mouse

Polb, encoding DNA polymerase β, is a member of the DNA polymerase X family. It is mainly involved in eukaryotic DNA replication, DNA damage repair (notably base excision repair-BER), gene recombination, and cell cycle regulation [1]. POLB's role in maintaining genome stability through BER is crucial for normal cellular function.

In mouse models, the POLB-Y265C mutation, resulting in an aberrant immune repertoire, leads to lupus-like disease. Mice with this mutation develop high levels of antinuclear antibodies, severe glomerulonephritis, and have shorter immunoglobulin heavy-chain junctions with increased somatic hypermutation [2,3,4]. Additionally, in MMR-deficient acute lymphoblastic leukemia cells, POLB plays a critical role in survival and thiopurine resistance. Depletion of POLB or treatment with its inhibitor oleanolic acid causes synthetic lethality, increasing cellular AP sites, DNA strand breaks, and apoptosis [5].

In conclusion, Polb is essential for DNA repair processes, especially BER. Mouse models with POLB mutations have been instrumental in revealing its role in autoimmune diseases like lupus and in understanding its contribution to drug resistance mechanisms in acute lymphoblastic leukemia. These findings enhance our understanding of the biological functions of Polb and offer potential therapeutic targets for related diseases.