Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.

TLDR

Down syndrome results from a 1.5‑fold increase in expression of genes on chromosome 21. The study created transgenic mice carrying the human Cu/Zn‑superoxide dismutase gene to serve as an animal model for investigating dosage effects in Down syndrome and the enzyme’s role in other pathologies. These mice express the human gene with 0.9‑ and 0.7‑kb transcripts in a 1:4 ratio and produce active enzyme capable of forming human‑mouse heterodimers. Brain SOD activity rose 1.6‑ to 6.0‑fold in the four transgenic strains, with similar or lesser increases in other tissues.

Abstract

Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. These animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.