Biomaterial Database

Amplification of a SV40 T antigen transgene is associated with sarcomagenesis in mice. 1994

T Teitz, and T S Yen, and Y W Kan

Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.

Transgenic mice harboring simian virus 40 large T antigen (Tag) gene fused to an erythroid-specific enhancer developed soft tissue sarcomas which expressed very high levels of T antigen. The Tag expression was not detectable in the animals' non-transformed tissues. While mice bearing several copies of the transgene developed tumors at an early age of 4-6 months, those with a single copy had a delayed onset of 10-16 months, and DNA analysis of their tumors showed amplification of the Tag transgene. Amplification of a Tag transgene has also been described previously in brain tumors. Our studies demonstrate that Tag transgene amplification is not restricted to a particular construct or a single tumor type. Therefore, this may be a general mechanism for Tag-mediated carcinogenesis, and our transgenic mouse system can be useful for elucidating the mechanisms that govern the amplification process of Tag sequences in vivo.

UI	MeSH Term	Description	Entries
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
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D012091	Repetitive Sequences, Nucleic Acid	Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).	DNA Repetitious Region,Direct Repeat,Genes, Selfish,Nucleic Acid Repetitive Sequences,Repetitive Region,Selfish DNA,Selfish Genes,DNA, Selfish,Repetitious Region, DNA,Repetitive Sequence,DNA Repetitious Regions,DNAs, Selfish,Direct Repeats,Gene, Selfish,Repeat, Direct,Repeats, Direct,Repetitious Regions, DNA,Repetitive Regions,Repetitive Sequences,Selfish DNAs,Selfish Gene
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D004273	DNA, Neoplasm	DNA present in neoplastic tissue.	Neoplasm DNA
D005784	Gene Amplification	A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.	Amplification, Gene
D005814	Genes, Viral	The functional hereditary units of VIRUSES.	Viral Genes,Gene, Viral,Viral Gene
D005914	Globins	A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.	Globin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000952	Antigens, Polyomavirus Transforming	Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.	Polyomavirus Large T Antigens,Polyomavirus Middle T Antigens,Polyomavirus Small T Antigens,Polyomavirus T Proteins,Polyomavirus Transforming Antigens,Polyomavirus Tumor Antigens,SV40 T Antigens,SV40 T Proteins,Simian Sarcoma Virus Proteins,Polyomaviruses Large T Proteins,Polyomaviruses Middle T Proteins,Polyomaviruses Small T Proteins,Antigens, Polyomavirus Tumor,Antigens, SV40 T,Proteins, Polyomavirus T,Proteins, SV40 T,T Antigens, SV40,T Proteins, Polyomavirus,T Proteins, SV40,Transforming Antigens, Polyomavirus,Tumor Antigens, Polyomavirus