Open AccessCorrection of mouse ornithine transcarbamytase deficiency by gene transfer into the germ line
Author(s) -
Catherine Cavard,
G. Grimber,
Nathalie Dubois,
Jean-François Chassé,
Myriam Bennoun,
Michèle Minet-Thuriaux,
P. Kamoun,
Pascale Briand
Publication year - 1988
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/16.5.2099
Subject(s) - ornithine transcarbamylase , ornithine transcarbamylase deficiency , biology , orotic acid , complementary dna , ornithine carbamoyltransferase , microbiology and biotechnology , microinjection , transgene , gene , phenotype , enzyme , gene expression , heterologous expression , reversion , biochemistry , ornithine , urea cycle , recombinant dna , endocrinology , arginine , amino acid
The sparse fur with abnormal skin and hair (Spf-ash) mouse is a model for the human X-linked hereditary disorder, ornithine transcarbamylase (OTC) deficiency. In Spf-ash mice, both OTC mRNA and enzyme activity are 5% of control values resulting in hyperammonemia, pronounced orotic aciduria and an abnormal phenotype characterized by growth retardation and sparse fur. Using microinjection, we introduced a construction containing rat OTC cDNA linked to the SV40 early promoter into fertilized eggs of Spf-ash mice. The expression of the transgene resulted in the development of a transgenic mouse whose phenotype and orotic acid excretion are fully normalized. Thus, the possibility of correcting hereditary enzymatic defect by gene transfer of heterologous cDNA coding for the normal enzyme has been demonstrated.