Mouse uroporphyrinogen decarboxylase: CDNA cloning, expression, and mapping

Abstract

Uroporphyrinogen decarboxylase (URO-decarboxylase; EC 4.1.1.37), the heme biosynthetic enzyme responsible for the conversion of uroporphyrinogen III to coproporphyrinogen III, is the enzymatic defect in porphyria cutanea tarda, the most common porphyria. The mouse URO-decarboxylase cDNA was isolated from a mouse adult liver cDNA library. The longest clone of 1.5 kb, designated pmUROD-1, had 5' and 3' untranslated sequences of 281 and 97 bp, respectively, and an open reading frame of 1104 bp encoding a 367-amino acid polypeptide with a predicted molecular mass of 40,595 Da. The mouse and human coding sequences had 87.8% and 90.0% nucleotide and amino acid identity, respectively. The authenticity of the mouse cDNA was established by expression of the active enzyme in Escherichia coli. In addition, the analysis of two sets of multilocus genetic crosses localized the mouse gene, Urod, on Chromosome (Chr) 4, consistent with the map location of the human gene to a position of conserved synteny on Chr 1. The availability of the mouse URO-decarboxylase should facilitate studies of the structure and organization of the mouse genomic sequence and the development of a mouse model of this inherited porphyria.

A zebrafish model for hepatoerythropoietic porphyria

“…The gene encoding UROD has been isolated from human, mouse, rat, yeast and bacteria [4][5][6][7][8][9] . Mutations responsible for reduced UROD activity have recently been identified in both PCT and HEP patients 3,10-17 .…”

Coexistence of a systemic lupus erythematosus and porphyria cutanea tarda: case successfully improved by avoidance of sun exposure

“…have suggested possible explanations for the coexistence of LE and porphyria: a common genetic abnormality, porphyria triggering an autoimmune response, preexisting LE resulting in an acquired metabolic fault leading to porphyria, and LE precipitating a genetically determined metabolic fault resulting in porphyria. 5 It is interesting that the gene for UROD is located on chromosome 1, 6 and that the 1q41-q42 region of that chromosome is probably linked to SLE. 7 Our patient did not drink much alcohol, take oral contraceptives, nor had any blood transfusions.…”

“…preexisting LE resulting in an acquired metabolic fault leading to porphyria, and LE precipitating a genetically determined metabolic fault resulting in porphyria (5). It is interesting that the gene for UROD is located on chromosome 1 (6), and that the 1q41-q42 region of that chromosome is probably linked to SLE (7).…”

A mouse model of familial porphyria cutanea tarda

“…The URO-D gene has been cloned and characterized from many species, and there is strong amino acid sequence homology among species (2,18). A murine URO-D cDNA has been cloned (19), but the mouse URO-D genomic locus has not yet been characterized.…”