Nthl1-flox Mouse

NTHL1, a DNA glycosylase, is crucial for maintaining genomic integrity as it is involved in the base excision repair machinery. This machinery removes approximately 30,000 base lesions per cell daily, highlighting the significance of NTHL1 in DNA repair [1].

Genetic studies have revealed that NTHL1 is a recessive cancer susceptibility gene. Homozygous mutations in NTHL1, such as c.244C>T p.(Gln82Ter), are associated with a high risk of breast, colorectal, urinary tract, and basal-cell skin cancers, while heterozygous mutations confer a lower risk of breast cancer [2]. Biallelic mutations in NTHL1 are associated with NTHL1-associated polyposis (NAP), a rare tumor syndrome, which also increases the risk of adenomatous polyposis and colorectal cancer. The spectrum of benign and malignant tumors in NTHL1-associated tumour syndrome is broader compared to other related syndromes [3]. A systematic review showed a high frequency of early-onset colorectal and breast cancers in patients with NTHL1 tumor syndrome, suggesting the need for cancer screening programs for NTHL1 biallelic carriers [4].

In conclusion, NTHL1 plays a vital role in maintaining genomic integrity through its function in base excision repair. Its malfunction, especially due to biallelic or homozygous mutations, is strongly associated with an increased risk of various cancers, including colorectal and breast cancers. Understanding NTHL1's function provides insights into the mechanisms of cancer development and could potentially guide the implementation of preventive and surveillance strategies for mutation carriers.