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

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-Cpoxnct mouse carries a hypomorphic mutation in the Cpox gene. Due to the mutation, BALB.NCT-Cpoxnct had a drastic increase in coproporphyrin in the blood and liver persistently from a young age. In this study, we found that BALB.NCT-Cpoxnct mice manifested HCP symptoms. Similar to HCP patients, BALB.NCT-Cpoxnct 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-Cpoxnct 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-Cpoxnct lacked these hepatic and cutaneous pathologies. In addition, we discovered that BALB.NCT-Cpoxnct exhibited microcytic anemia. These results indicate that BALB.NCT-Cpoxnct mice serve as the suitable animal model to help gain insight into the pathogenesis and therapy of HCP.