Abstract
In humans, mutations in the coproporphyrinogen oxidase (CPOX) gene can result in hereditary coproporphyria (HCP), characterized by high levels of coproporphyrin excretion in the urine and feces, as well as acute neurovisceral and chronic cutaneous manifestations. Appropriate animal models for comprehending the precise pathogenesis mechanism of HCP have not been reported that show similarities in terms of gene mutation, reduced CPOX activity, excess coproporphyrin accumulation, and clinical symptoms. As previously discovered, the BALB.NCT-Cpox nct mouse carries a hypomorphic mutation in the Cpox gene. Due to the mutation, BALB.NCT-Cpox nct had a drastic increase in coproporphyrin in the blood and liver persistently from a young age. In this study, we found that BALB.NCT-Cpox nct mice manifested HCP symptoms. Similar to HCP patients, BALB.NCT-Cpox nct excreted an excessive amount of coproporphyrin and porphyrin precursors in the urine and displayed neuromuscular symptoms, such as a lack of grip strength and impaired motor coordination. Male BALB.NCT-Cpox nct had nonalcoholic steatohepatitis (NASH)-like liver pathology and sclerodermatous skin pathology. A portion of male mice had liver tumors as well, whereas female BALB.NCT-Cpox nct lacked these hepatic and cutaneous pathologies. In addition, we discovered that BALB.NCT-Cpox nct exhibited microcytic anemia. These results indicate that BALB.NCT-Cpox nct mice serve as the suitable animal model to help gain insight into the pathogenesis and therapy of HCP.