Heme biosynthesis is a complex multistep process, taking place partly in the cytosol and partly in the mitochondria. A dysfunction of one or more enzymes in the biochemical pathway results in the accumulation of intermediates of the porphyrin synthesis and to the onset of porphyrias. Porphyrias are mainly hereditary; however, they can also be induced by exogenous factors. Depending on which enzyme of the heme biosynthesis is defective, different types of porphyrias can be discriminated (Phillips et al., 2001). Porphyria cutanea tarda (PCT), caused by a defect of the uroporphyrinogen decarboxylase, is a chronic hepatic porphyria and most often the form of porphyrias in man (Egger et al., 2002). Uroporphyrinogen decarboxylase (UROD) catalyzes the synthesis of copro-porphyrinogen III from uroporphyrinogen III by a stepwise decarboxylation of acetic acids. The clinical signs of PCT are caused by the reduced UROD activity that results in an increase of uroand heptacarboxyporphyrin in the liver (Elder, 1998). These and other metabolites are then excreted in the urine and faeces (Poh-Fitzpatrick, 1998). The presence of porphyrins in the urine leads to a brown discolouring. The highly carboxylated uroand heptacarboxyporphyrin are mainly found in the urine, whereas porphyrins with 4, 5, or 6 carboxyl groups are less abundant (Poh-Fitzpatrick, 1993). In the liver, deposition of porphyrins results in an inflammation of hepatocytes, fibrosis and hemosiderosis. Once the storage capacity of the liver is exhausted, porphyrins are also deposited in the skin resulting in Fig. 1. FISH mapping of the ovine UROD gene. Specific signals were detected on chromosome 1p34→p36 (arrow).

s O1–O4 Page 12 Animal molecular cytogenetics