Slc22a2-flox Mouse

Slc22a2, encoding the organic cation transporter-2 (OCT2), is a polyspecific transporter in the SLC22 family. It mediates the electrogenic transport of small organic cations with different molecular structures, and is expressed in tissues like the kidney and liver. SLC22 transporters, including Slc22a2, are involved in regulating key metabolic pathways and levels of signaling molecules, and play important roles in interorgan and interorganism small-molecule communication [3,4].

In patients with colorectal cancer receiving oxaliplatin chemotherapy, the rs316019 genotype of Slc22a2 was significantly associated with the severity of leucopenia and neutropenia, and the rs1869641 genotype was associated with the occurrence of thrombocytopenia [1]. In HIV-positive patients treated with dolutegravir, the SLC22A2 CA genotype was independently associated with an abnormal general severity index, anxiety, hostility, and moderate to severe headache [2]. In renal transplantation, SLC22A2 was associated with phenotypes of net tubular creatinine secretion and end-stage renal disease [5]. Also, the rs316019 (p.270A > S) variant of SLC22A2 may reduce the clearance of metformin from circulation, potentially leading to metformin-associated lactic acidosis [6].

In conclusion, Slc22a2 is crucial for the transport of various organic cations, which impacts drug efficacy, toxicity, and metabolic processes. Studies on its genetic variants in different patient populations have revealed its associations with hematological toxicity in colorectal cancer chemotherapy, psychiatric symptoms in HIV patients on dolutegravir, creatinine handling in renal transplantation, and metformin clearance in type 2 diabetes. These findings contribute to understanding the role of Slc22a2 in disease-related drug responses and metabolic regulations.