Resistance to influenza virus infection of Mx transgenic mice expressing Mx protein under the control of two constitutive promoters

Kolb, E.; Laine, Elisabeth; Strehler, D; Staeheli, Peter

doi:10.1128/jvi.66.3.1709-1716.1992

Cited by 37 publications

(12 citation statements)

References 28 publications

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“…The resistance is apparently virus specific since the same cells remained susceptible to the lethal effects of infection by the rhabdovirus, VSV; the togavirus Semliki Forest virus (SFV); two picornaviruses, Mengo and encephalomyocarditis virus (EMGV); and a herpesvirus, herpes simplex virus 1 (HSV-1). Similar results were observed for BALB.A2G-Mxl mice carrying the Mxl gene in the BALB/c background (70) and transgenic mice and pigs carrying cDNA copies of the murine Mxl protein (73,74).…”

Section: Antiviral Activity Of Cloned MX Proteinssupporting

confidence: 82%

Interferon‐inducible Mx proteins in fish

Leong

Trobridge

Kim

et al. 1998

Immunological Reviews

105

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Mx proteins are members of a family of interferon-inducible genes expressed when cells are treated with double-stranded RNA or virus infection. These proteins are important components of the antiviral response and form the first line of the body's defense against virus infections. The exact mechanism of action for these proteins has not been discovered, but mice missing the Mx genes are extremely sensitive to influenza virus infection. Mammals have between two and three Mx genes whose functions may vary with regard to the inhibition of a specific virus, cellular localization, and activity. The cDNA of three rainbow trout Mx proteins has been cloned and a comparison of their sequences with that of avian and mammalian species reveals striking conservation of domains. They all maintain the tripartite ATP/GTP binding domain and the dynamin family signature in the amino terminal half of the protein. In the carboxyl terminal half of the Mx proteins are the localization signals and the leucine zipper motifs which account for the trimerization of Mx in the cell. Like the rat and human Mx proteins, the different trout Mx proteins exhibit distinctly different immunohistochemical staining patterns in cells transfected with plasmids expressing RBTMx1, RBTMx2, or RBTMx3. To date, the antiviral function of the trout Mx proteins has not been satisfactorily established.

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Section: Antiviral Activity Of Cloned MX Proteinssupporting

confidence: 82%

Interferon‐inducible Mx proteins in fish

Leong

Trobridge

Kim

et al. 1998

Immunological Reviews

105

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“…permit ubiquitous expression of transgenes in mice (10,20). Our results suggest that constitutive expression of MxA in certain organs is deleterious, as has been suggested for the mouse Mx1 protein (2,3,17). It should be noted that a construct that permits MxA synthesis under the control of the IFN-regulated promoter of the mouse Mx1 gene gave no improvement: 8 of the 10 transgenic mice that carried this construct failed to express MxA after treatment with an IFNinducing substance.…”

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confidence: 53%

“…Mice devoid of functional Mx genes would thus seem to represent an ideal experimental system for testing the antiviral activities of Mx proteins in vivo. The great potential of this system was emphasized by the recent demonstration that transgenic expression of the wild-type form of mouse Mx1 cDNA rendered such mice resistant to challenges with influenza A virus (3,17) and Thogoto virus (12).…”

mentioning

confidence: 99%

“…The 8-kb NotI restriction fragment was excised from pHMG-MxA (30) and purified by agarose gel electrophoresis. Microinjection of DNA into the pronuclei of fertilized eggs from (C57BL/6 ϫ SJL)F 2 mice was done as described previously (17). To test whether MxA rendered cells from transgenic mice resistant to virus infection, we prepared cultures of embryonic fibroblasts from transgenic L mice and nontransgenic controls and challenged the confluent cell monolayers with several RNA viruses as described previously (30).…”

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confidence: 99%

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Enhanced virus resistance of transgenic mice expressing the human MxA protein

Pavlovic

Arzet

Hefti

et al. 1995

J Virol

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116

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MxA is a GTPase that accumulates to high levels in the cytoplasm of interferon-treated human cells. Expression of MxA cDNA confers to transfected cell lines a high degree of resistance against several RNA viruses, including influenza, measles, vesicular stomatitis, and Thogoto viruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promoter. Embryonic fibroblasts derived from the transgenic mice were nonpermissive for Thogoto virus and showed reduced susceptibility for influenza A and vesicular stomatitis viruses. The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or intraperitoneal route. Furthermore, the transgenic mice were more resistant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demonstrate that MxA is a powerful antiviral agent in vivo, indicating that it may protect humans from the deleterious effects of infections with certain viral pathogens.

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“…The mouse Mxl protein, and its human homologue M A , are nuclear proteins capable of protecting cultured cells against the influenza virus (62 (67). Under the regulation of the HMG-CoA promoter, the protein was expressed constitutively in the brain.…”

Section: Resistance Of M X L Transgenic Mice To Infection With a Neurmentioning

confidence: 99%

Transgenic and Knock‐out Mice: Models of Neurological Disease

et al. 1994

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Besides providing useful model systems for basic science, studies based on modification of the mammalian germ line are changing our understanding of pathogenetic principles. In this article, we review the most popular techniques for generating specific germ line mutations in vivo and discuss the impact of various transgenic models on the study of neurodegenerative diseases. The “gain of function” approach, i.e., ectopic expression of exogenous genes in neural structures, has deepened our understanding of neurodegeneration resulting from infection with papova viruses, picorna viruses, and human retroviruses. Further, inappropriate expression of mutated cellular molecules in the nervous system of transgenic mice is proving very useful for studying conditions whose pathogenesis is controversial, such as Alzheimer's disease and motor neuron diseases. As a complementary approach, ablation of entire cell lineages by tissue‐specific expression of toxins has been useful in defining the role of specific cellular compartments. Modeling of recessive genetic diseases, such as Lesch‐Nyhan syndrome, was helped by the development of techniques for targeted gene deletion (colloquially termed “gene knock‐out”). Introduction of subtle homozygous mutations in the mouse genome was made possible by the latter approach. Such “loss of function” mutants have been used for clarifying the role of molecules thought to be involved in development and structural maintenance of the nervous system, such as the receptors for nerve growth factor and the P0 protein of peripheral myelin. In addition, these models are showing their assets also in the study of enigmatic diseases such as spongiform encephalopathies.

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Resistance to influenza virus infection of Mx transgenic mice expressing Mx protein under the control of two constitutive promoters

Cited by 37 publications

References 28 publications

Interferon‐inducible Mx proteins in fish

Interferon‐inducible Mx proteins in fish

Enhanced virus resistance of transgenic mice expressing the human MxA protein

Transgenic and Knock‐out Mice: Models of Neurological Disease

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