Characterization of transgenic mice containing adenovirus early region 3 genomic DNA

G. Fejer, I. Gyory, J. Tufariello, M. S. Horwitz

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Human adenoviruses (Ad) contain a complex transcription region (E3) which codes for proteins that interact with several arms of the immune system. However, E3 genes are not essential for replication in tissue culture. An E3- encoded 19,000-molecular-weight (19K) glycoprotein (gp19K) binds to the class I major histocompatibility complex (MHC) in the endoplasmic reticulum and prevents MHC transport to the cell surface. Three other E3 proteins are involved in the inhibition of apoptosis by tumor necrosis factor alpha. The entire E3 genomic DNA was utilized to produce transgenic mice to study the effect of the E3 proteins on pathogenesis of various infectious agents and to investigate the in vivo synthesis and processing of the multiple E3 mRNAs and proteins. There was basal expression of the E3 promoter in the thymus, kidneys, uterus, and testes and at all levels of the gastrointestinal tract. In addition, the E3 promoter of the transgene could be activated in some other organs, including the liver, by infection of these animals with an E3- deficient Ad (Ad7001) which contains a functional E1A region. Transactivation in vivo could also be demonstrated by infusion of bacterial lipopolysaccharide. There appeared to be differential ratios of expression between several of the E3 mRNAs in transgenic lung fibroblasts and primary kidney cells cultured from the transgenic animals. This observation suggested that there was differential mRNA splicing that was organ specific. These transgenic animals should provide a useful model for studying the effects of the E3 proteins on the immune system and on diseases affected either by control of MHC or by selected functions of tumor necrosis factor that are inhibitable by Ad E3 proteins.

Original languageEnglish (US)
Pages (from-to)5871-5881
Number of pages11
JournalJournal of Virology
Volume68
Issue number9
StatePublished - Sep 1994

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Adenoviridae
Transgenic Mice
genetically modified organisms
genomics
Major Histocompatibility Complex
DNA
mice
major histocompatibility complex
Genetically Modified Animals
transgenic animals
Proteins
proteins
Adenovirus E3 Proteins
Messenger RNA
Tumor Necrosis Factor-alpha
immune system
Kidney
Human Adenoviruses
promoter regions
Essential Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Fejer, G., Gyory, I., Tufariello, J., & Horwitz, M. S. (1994). Characterization of transgenic mice containing adenovirus early region 3 genomic DNA. Journal of Virology, 68(9), 5871-5881.

Characterization of transgenic mice containing adenovirus early region 3 genomic DNA. / Fejer, G.; Gyory, I.; Tufariello, J.; Horwitz, M. S.

In: Journal of Virology, Vol. 68, No. 9, 09.1994, p. 5871-5881.

Research output: Contribution to journalArticle

Fejer, G, Gyory, I, Tufariello, J & Horwitz, MS 1994, 'Characterization of transgenic mice containing adenovirus early region 3 genomic DNA', Journal of Virology, vol. 68, no. 9, pp. 5871-5881.
Fejer G, Gyory I, Tufariello J, Horwitz MS. Characterization of transgenic mice containing adenovirus early region 3 genomic DNA. Journal of Virology. 1994 Sep;68(9):5871-5881.
Fejer, G. ; Gyory, I. ; Tufariello, J. ; Horwitz, M. S. / Characterization of transgenic mice containing adenovirus early region 3 genomic DNA. In: Journal of Virology. 1994 ; Vol. 68, No. 9. pp. 5871-5881.
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