title: Ferrochelatase structural mutant (Fechm1Pas) in the house mouse.
abstract: The molecular basis of an inherited defect of ferrochelatase in mouse (Fechm1Pas/Fechm1Pas, described by Tutois et al., 1991, J. Clin. Invest. 88:1730-1736) was investigated. cDNA clones encoding ferrochelatase, isolated by amplification of the mRNA from the liver of a mutant mouse using the polymerase chain reaction, were sequenced by the dideoxynucleotide chain-termination method. All the clones carried a T to A transversion at nucleotide 293, leading to a methionine to lysine substitution at position 98 in the protein (mutation M98K). Hybridization with allele-specific oligonucleotides (ASOs) confirmed the mutation at the cDNA and genomic levels. Finally, expression of the mutant ferrochelatase protein in E. coli demonstrated a marked deficiency in activity in agreement with the activity of the deficient enzyme in vivo. This Fechm1Pas/Fechm1Pas mutant mouse represents a useful model for studying the pathophysiological feature of the human disease and the first accessible model for gene therapy in the field of porphyrias.
authors.affiliation: Laboratoire de Génétique Moléculaire, Faculté X. Bichat, Université Paris 7, France.
authors.forename: S
authors.initials: S
authors.lastname: Boulechfar
authors.forename: J
authors.initials: J
authors.lastname: Lamoril
authors.forename: X
authors.initials: X
authors.lastname: Montagutelli
authors.forename: J L
authors.initials: JL
authors.lastname: Guenet
authors.forename: J C
authors.initials: JC
authors.lastname: Deybach
authors.forename: Y
authors.initials: Y
authors.lastname: Nordmann
authors.forename: H
authors.initials: H
authors.lastname: Dailey
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: H
authors.initials: H
authors.lastname: de Verneuil
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D004926:Escherichia coli; D005294:Ferrochelatase / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D046351:Protoporphyria, Erythropoietic
chemical_list: D004247:DNA; D005294:Ferrochelatase