Characterization of phenotypes resulting from a BSE/scrapie co-infection of ovine PrP overexpessing transgenic mice (Tgshp IX)
Christine FastMartin EidenIsabelle LantierPatricia BerthonFrédéric LantierMarkus KellerOlivier AndréolettiMartin H. Groschup
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The use of the Cre-loxP recombination system allows the conditional inactivation of genes in mice. The availability of transgenic mice in which the Cre recombinase expression is highly cell type specific is a prerequisite to successfully use this system. We previously have characterized regulatory regions of the mouse flk-1 gene sufficient for endothelial cell-specific expression of the LacZ reporter gene in transgenic mice. These regions were fused to the Cre recombinase gene, and transgenic mouse lines were generated. In the resulting flk-1-Cre transgenic mice, specificity of Cre activity was determined by cross-breeding with the reporter mouse lines Rosa26R or CAG-CAT-LacZ. We examined double-transgenic mice at different stages of embryonic development (E9.5-E16.5) and organs of adult animals by LacZ staining. Strong endothelium-specific staining of most vascular beds was observed in embryos older than E11.5 in one or E13.5 in a second line. In addition, the neovasculature of experimental BFS-1 tumors expressed the transgene. These lines will be valuable for the conditional inactivation of floxed target genes in endothelial cells of the embryonic vascular system.
Cre recombinase
Gene targeting
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We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the beta-actin locus. Mice that are hemizygous for this transgene express normal levels of beta-actin and higher levels of SIRT1 protein in several tissues. Transgenic mice display some phenotypes similar to mice on a calorie-restricted diet: they are leaner than littermate controls; are more metabolically active; display reductions in blood cholesterol, adipokines, insulin and fasted glucose; and are more glucose tolerant. Furthermore, transgenic mice perform better on a rotarod challenge and also show a delay in reproduction. Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity.
Calorie Restriction
Sirtuin 1
Transgenesis
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Transgenic mice are an important in vivo model for studying the function of single genes. Specific induction and tissue specific expression of the inserted genes are the great advantages of this system. However, there a risks in constructing transgenic mice and the interpretion of the experimental data. To prevent artefacts and to optimize the transgenic model, the experimental systems have to fulfill the following presets:
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Characterization
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Summary The UAS-A42 H29.3 transgenic Drosophila line used to model Alzheimer type neurodegeneration and other phenotypes falls down when transitioned from a light to a dark environment. This unusual phenotype is not dependent on the presence of a Gal4 driver and is thus unrelated to A42 induced proteotoxicity or neurodegeneration. We propose that it may instead be the result of disruption in another gene function caused by the P element insertion site. Since this transgenic line is used by several groups to analyze neurological phenotypes associated with A42 neuronal expression, the results of these studies must be interpreted with caution.
Proteotoxicity
Loss function
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What are transgenic mice and what do we learn from them? In this review, we focus on the generation of "classical" transgenic and "knock-out" mice. The establishment of transgenic and gene-targeted mice provides an unique tool to study the function(s) of a given gene in the context of a whole organism. Based on selected examples, we demonstrate the potential of this transgenic technology to understand the interactions between cells, organs and organ systems in genetically engineered mice.
Model Organism
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Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interactions using multiple fluorescent proteins in the same mouse, and the cell cycle in real time and in the whole animal, and they can be used to perform deep tissue imaging in the whole animal, follow cell lineage during development and disease, and isolate large quantities of a pure cell type directly from organs. These novel transgenic mice and their applications provide the means for studying of molecular and biochemical events in the whole animal that was previously limited to cell cultures. In conclusion, transgenic mice are not just for generating knockouts.
Gene knockout
Cre recombinase
Knockout mouse
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Conditional gene knockout
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Pathogenesis
Transmissible spongiform encephalopathy
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