Retroviruses and embryogenesis: Microinjection of Moloney leukemia virus into midgestation mouse embryos

Jaenisch, Rudolf

doi:10.1016/0092-8674(80)90399-2

Cited by 144 publications

(88 citation statements)

References 10 publications

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“…Nevertheless, our observations do indicate that the specific stage of differentiation has a major role in regulating virus production by cells cultured from human testicular germ-cell tumours, an effect recognized in other cell-virus systems (e.g. see Jaenisch, 1980;Liebermann et al, 1980;Maltzman & Levine, 1981).…”

Section: Discussionmentioning

confidence: 86%

Production of Virions with Retrovirus Morphology by Human Embryonal Carcinoma Cells in vitro

Bronson

Saxinger

Ritzi

et al. 1984

Journal of General Virology

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SUMMARYEmbryonal carcinoma (EC) cell lines established from human testicular germ-cell tumours produce, at low frequency, virions morphologically identical to type C retroviruses that have been observed by other workers in human placental tissues. The virus particles are formed while budding from the cell surface, and their numbers are increased by inducing the EC ceils with 5-iodo-2'-deoxyuridine and dexamethasone. Assays for RNA-dependent DNA polymerase (reverse transcriptase) associated with purified virions suggested a low level of activity. In addition, another type of virus is occasionally produced by induced cells of three EC lines. These particles also form during the process of budding from the cell surface, but they have surface projections (spikes). Extracellular spiked virions frequently are pleomorphic, with a condensed, eccentric nucleoid, and thus morphologically resemble type B retroviruses. No virions of either type were detected with or without induction in cultures of differentiated EC cells or in cultures of yolk sac carcinoma or teratoma cells, both of which are considered malignant but differentiated derivatives of EC cells. The lack of virion production by these differentiated cells suggests developmental regulation of virus replication.

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Section: Discussionmentioning

confidence: 86%

Production of Virions with Retrovirus Morphology by Human Embryonal Carcinoma Cells in vitro

Bronson

Saxinger

Ritzi

et al. 1984

Journal of General Virology

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“…One of our major interests is to use the vectors to introduce and express foreign genes in somatic tissues of developing mouse embryos. It has been shown that wild-type Mo-MLV can replicate unrestricted in most somatic tissues when introduced at the postimplantation stage between days 8 and 10 of gestation (12,13). However, replication-defective vectors carrying a dominant selectable marker, either in combination with a helper virus or alone, resulted in insertion of the marker gene in only a small fraction of cells from different organs, which indicates the need for virus spread (28; H. Stuhlmann, R. Jaenisch, and R. C. Mulligan, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Construction and properties of replication-competent murine retroviral vectors encoding methotrexate resistance.

1989

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A series of replication-competent Moloney murine leukemia virus vectors was constructed in which each vector contained a mutant dihydrofolate reductase (DHFR) cDNA insert in the U3 region of the viral long terminal repeat. Two of the resulting viruses, MLV (murine leukemia virus) DHFR*-5 and MLV DHFR*-7, were able to stably transfer methotrexate resistance to infected fibroblast cells upon multiple rounds of virus replication and in the absence of drug selection. Cell lines producing recombinant virus with high titers were established, which indicated that the insert did not grossly interfere with viral replication functions. These vectors should be useful for introducing and expressing foreign genes in vivo in tissues and whole animals in which virus spread is needed for efficient infection.

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“…Transgenic mice may be created 'classically' through (1) direct pro-nuclear injection of exogenous DNA into fertilized zygotes (Gordon and Ruddle, 1983;Brinster et al, 1985;Palmiter and Brinster, 1986), implantation into a pseudo-pregnant female-generating transgenic progeny or (2) via injection of genetically modified mouse embryonic stem (ES) cells into a blastocyst (Doetschman et al, 1985;Gossler et al, 1986;Robertson et al, 1986) (embryonic day 4.5) with (3) embryonic retroviral infection (Jaenisch, 1980;Jaenisch et al, 1981;Soriano and Jaenisch, 1986), representing a further alternative. While direct pronuclear injection of exogenous DNA results in indiscriminate integration into the genome and is reliant upon overexpression of the transgene to generate a phenotype, ES cells can be genetically tailored via homologous recombination (Smithies et al, 1985) (that is location and enzymatic recombination of an exogenous DNA fragment into the homologous endogenous sequence; Figure 1a and Supplementary Information) in vitro prior to blastocoel insertion, representing the superior technique.…”

Section: Transgenic Micementioning

confidence: 99%

Review: genetic models of acute myeloid leukaemia

2008

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The use of genetically engineered mice (GEM) have been critical in understanding disease states such as cancer, and none more so than acute myelogenous leukaemia (AML), a disease characterized by over 100 distinct chromosomal translocations. A substantial proportion of cases exhibiting recurrent reciprocal translocations at diagnosis, such as t(8;21) or t(15;17) have been exhaustively studied and are currently employed in clinical diagnosis. However, a definitive conclusion regarding the leukaemogenic potential of defined transgenes for this disease remains elusive. While it is increasingly apparent that a number of cooperating mutations are necessary to develop a leukaemic phenotype, the number of models reflecting these synergisms remains few. Furthermore, little emphasis has been paid to the effect of chromosomal translocations other than recurrent genetic abnormalities, with no models reflecting the multiple abnormalities observed in high-risk cases of AML accounting for 8-10% of adult AML. Here we review the differing technologies employed in generation of GEM of AML. We discuss the relevance of GEM AML from embryonic stem cell-mediated (for example retinoic acid receptor-a fusions and AML1/ETO) models; through to the valuable retroviral-mediated gene transfer models. The latter have been used to great effect in defining the transforming properties of chromosomal translocation products such as MLL (found in 5-6% of all AML cases) and NUP98 (denoting poor prognosis in therapy-related disease) and particularly when co-transduced with bad prognostic factors such as Flt3 mutations. Finally, we comment on the emergence of newer transduction technologies, which can regulate the level of expression to defined cell lineages in both primary murine and human xenografts, and discuss how combining multiple genetic modalities, more relevant models of this complex disease are being generated.

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Retroviruses and embryogenesis: Microinjection of Moloney leukemia virus into midgestation mouse embryos

Cited by 144 publications

References 10 publications

Production of Virions with Retrovirus Morphology by Human Embryonal Carcinoma Cells in vitro

Production of Virions with Retrovirus Morphology by Human Embryonal Carcinoma Cells in vitro

Construction and properties of replication-competent murine retroviral vectors encoding methotrexate resistance.

Review: genetic models of acute myeloid leukaemia

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