Pold1-flox Mouse

POLD1, encoding the catalytic and proofreading subunit of DNA polymerase δ, is crucial for DNA replication and proofreading [1,2,4,5]. It is involved in maintaining genomic stability, a key process in normal cellular function and development. Genetic models, such as KO or CKO mouse models, could potentially be used to further explore its functions in vivo.

Germline pathogenic variants in the exonuclease domain of POLD1 predispose to adenomatous polyps, colorectal cancer, endometrial tumors, and other malignancies, with an increased mutation rate and specific mutational signatures [2]. POLD1 mutations also define a rare subtype of ultramutated metastatic colorectal cancer, and patients with such mutations show more favorable outcomes to immune checkpoint inhibitor treatment compared to mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer [6]. Additionally, high POLD1 expression promotes the proliferation and metastasis of bladder cancer via stabilizing MYC, forming a positive feedback loop with MYC [3].

In conclusion, POLD1 is essential for DNA replication and proofreading, playing a significant role in maintaining genomic stability. Its mutations are associated with an increased risk of various cancers, and understanding POLD1 through model-based research, such as potential KO/CKO mouse models, may provide insights into cancer development and treatment, especially in relation to immunotherapy and the role in specific cancer types like colorectal and bladder cancer [2,3,6].