BALB.NCT-Cpox is a unique mouse model of hereditary coproporphyria

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 mouse carries a hypomorphic mutation in the Cpox gene. Due to the mutation, BALB.NCT-Cpox 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 mice manifested HCP symptoms. Similar to HCP patients, BALB.NCT-Cpox 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 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 lacked these hepatic and cutaneous pathologies. In addition, we discovered that BALB.NCT-Cpox exhibited microcytic anemia. These results indicate that BALB.NCT-Cpox mice serve as the suitable animal model to help gain insight into the pathogenesis and therapy of HCP.