The disruption of mouse uroporphyrinogen III synthase (uros) gene is fully lethal

Congenital erythropoietic porphyria (CEP) is a recessive autosomic disorder characterized by a deficiency in uroporphyrinogen III synthase (UROIIIS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment and the knowledge of the molecular lesions are strong arguments Ibr gene therapy. An animal model of CEP was designed in order to evaluate the feasibility of retroviral gene transfer in hematopoietic cells. A null allele of the mouse uros gene (uros(del)) was obtained by targeted mutagenesis in embryo-derived stem cells (ES cells). A replacement vector containing a disruption of the eighth exon of the uros gene was constructed and introduced into ES cells. After blastocyst microinjection and breeding experiments, no homozygous mutant mouse was viable, even at early stages of development. We conclude that the presence of a null allele of the uros gene is lethal in mice.