Biomaterial Database

Mice with duplications and deletions at the Tme locus have altered MnSOD activity. 1994

E Wang, and G Cortopassi

Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033.

Superoxide radicals that result from normal cellular metabolism have been implicated as a cause of multiple age-related degenerative diseases (Halliwell, B., and Gutteridge, J. M. (1990) Methods Enzymol. 186, 1-85; Harman, D. (1988) Mol. Cell. Biochem. 84, 155-161; Ames, B. N., Shigenaga, M. K., and Hagen, T. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7915-7922). Manganese superoxide dismutase (MnSOD) is thought to be the sole enzymic scavenger of superoxide in mammalian mitochondria. We have investigated MnSOD activity and gene dose in mice with deletions and a duplication of the Tme (t-associated maternal effect) locus on chromosome 17. We find that MnSOD activity is significantly correlated with gene dose in these animals; animals with heterozygous deletions of Tme have 50% of normal activity, and animals with a heterozygous duplication of Tme have 150% of normal activity. These ratios of activity appear to be systemic, as they were observed in brain, heart, skeletal muscle and liver. The results support the model that basal MnSOD activity is regulated solely by cis elements, in that variation in MnSOD activity caused by altered gene dose on one chromosome is not compensated by gene activity on the other. Since gene knockouts of MnSOD have not yet been generated, the tlub2 and Thp animals may become useful models for those studying the role of mitochondrial superoxide in pathophysiological processes. A model for the maternal-lethal effect of Tme deletions is proposed.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002874	Chromosome Mapping	Any method used for determining the location of and relative distances between genes on a chromosome.	Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D005810	Multigene Family	A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)	Gene Clusters,Genes, Reiterated,Cluster, Gene,Clusters, Gene,Families, Multigene,Family, Multigene,Gene Cluster,Gene, Reiterated,Multigene Families,Reiterated Gene,Reiterated Genes
D006579	Heterozygote	An individual having different alleles at one or more loci regarding a specific character.	Carriers, Genetic,Genetic Carriers,Carrier, Genetic,Genetic Carrier,Heterozygotes