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

Journal Article · Sun Nov 01 00:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.22.8044· OSTI ID:6618358

Epstein, C J; Avraham, K B; Lovett, M; Smith, S; Elroy-Stein, O; Rotman, G; Bry, C; Groner, Y

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. The 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 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.

• Research Organization: Univ. of California, San Francisco (USA)
• OSTI ID: 6618358
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:22
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHROMOSOMAL ABERRATIONS
BIOLOGICAL MODELS
DOWNS SYNDROME
PATHOGENESIS
SUPEROXIDE DISMUTASE
BIOCHEMISTRY
COPPER COMPOUNDS
ENZYME ACTIVITY
HUMAN CHROMOSOME 21
HYBRIDIZATION
LIVER
MICE
PHOSPHORUS 32
ZINC COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CHEMISTRY
CHROMOSOMES
CONGENITAL MALFORMATIONS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GLANDS
HEREDITARY DISEASES
HETEROCHROMOSOMES
ISOTOPES
LIGHT NUCLEI
MALFORMATIONS
MAMMALS
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
ORGANS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RODENTS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
550401* - Genetics- Tracer Techniques