Abstract
The porphyrias are a group of metabolic disorders that are caused by defects in one
of the eight enzymes that synthesize heme. A common feature of all porphyrias is accumulation
of porphyrin precursors or porphyrins, which are intermediates of the heme biosynthesis
pathway. Approximately 15% of heme biosynthesis occurs in the liver, and excessive
hepatic production of porphyrin precursors caused by heme enzyme deficiencies can
lead to neurovisceral manifestations. Additionally, in erythropoietic protoporphyria,
porphyrins accumulate in the liver, leading to hepatic injury. These rare diseases
have few effective medical therapies, and disease mechanisms are not always well understood.
Animal models have provided a platform to study the pathophysiology of disease and
test emerging therapies. In this review, the last of a three-part series, we describe
the animal models that have been generated to study porphyrias with hepatic involvement.
For each model, we discuss mechanisms of injury, phenotypic features, and the similarities
and contrasts to human porphyria. We also describe preclinical studies that have utilized
the model for therapeutic interventions. Overall, animal-based studies have made significant
contributions to our understanding of porphyria and may lead to innovative therapies
in the future.
Keywords
acute intermittent porphyria - variegate porphyria - hereditary coproporphyria - porphyria
cutanea tarda - erythropoietic porphyria
