Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

Lemaire-Vieille, Catherine; Schulze, Tobias; Podevin-Dimster, Valérie; Follet, Jérôme; Bailly, Yannick; Blanquet-Grossard, Françoise; Decavel, Jean-Pierre; Heinen, Ernst; Cesbron, Jean‐Yves

doi:10.1073/pnas.080081197

Cited by 69 publications

(49 citation statements)

References 46 publications

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“…In a previous study, a green fluorescent protein reporter gene under the control of bovine PrP C gene regulatory sequences was expressed in the mucosal capillary endothelial cells of the intestine of transgenic mice (Lemaire-Vieille et al, 2000). Reporter gene expression in endothelial and epithelial cells strongly suggests that these cell types normally express the PrP C gene.…”

Section: Discussionmentioning

confidence: 96%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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Prion diseases are induced by pathologically misfolded prion protein (PrPSc ), which recruit normal sialoglycoprotein PrP C by a templatedirected process. In this study, we investigated the expression of PrP C in a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrP C -immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrP C protein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrP C protein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrP C by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrP C -Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrP C in the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrP C and activated extracellular signal-regulated kinase (ERK1/2) under hypoxia-reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia-reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrP C promoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3-to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrP C resulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrP C expression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrP C has physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

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Section: Discussionmentioning

confidence: 96%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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“…The prion promoter drives expression of the transgene in both lines. Whereas the prion promoter used in the present study has been considered to be primarily expressed in neurons, 29 prion protein expression is more ubiquitous and has also been reported in glial cells 30 -33 as well as epithelial and endothelial cells 34 of transgenic mice. Differences in the filamentous aggregates in neurons and oligodendrocytes may reflect differences in transgene expression in the different cell types.…”

Section: Discussionmentioning

confidence: 97%

Filamentous Tau in Oligodendrocytes and Astrocytes of Transgenic Mice Expressing the Human Tau Isoform with the P301L Mutation

Lin

Lewis

Yen

et al. 2003

The American Journal of Pathology

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We recently reported a transgenic mouse line (JNPL3) that expresses mutant (P301L) tau and develops neurofibrillary tangles composed of filamentous tau aggregates. Here we show that these mice have abnormal tau filaments not only in neurons, but also in oligodendrocytes and astrocytes. Similar results were detected in another transgenic line (JNPL2؉3؉) that expresses the longest human tau isoform with the P301L mutation. The ultrastructure of the tau filaments and immunoreactivity with tau and ubiquitin antibodies were similar in glia and neurons. Given similarities of the lesions in the mice to human neuronal and glial inclusions, these transgenic mice appear to be a valuable model to study pathogenesis of the neurodegenerative tauopathies.

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“…In the model of APP-Tg mice we used, the APP gene is expressed under the prion promoter (17). Recent work has shown that the expression of a reporter gene under the control of the bovine prion promoter occurs in additional tissues besides the brain, including the thymus (26). It is likely that chronic expression of APP in the brain and other organs and especially the substantial levels of A␤ in the blood lead to hyporesponsiveness of A␤-reactive T or B cells.…”

Section: Discussionmentioning

confidence: 99%

Immune hyporesponsiveness to amyloid β-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease

Monsonego

Maron

Zota

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

160

112

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Alzheimer's disease is a dementia that involves progressive deposition of amyloid ␤-protein (A␤) in brain regions important for memory and cognition, followed by secondary inflammation that contributes to the neuropathologic process. Immunization with A␤ can reduce cerebral A␤ burden and consequent neuropathologic changes in the brains of mice transgenic for the ␤-amyloid precursor protein (APP). We found that transgenic expression of human APP in B6SJL mice, under the prion promoter, results in immune hyporesponsiveness to human A␤, in terms of both antibody and cellular immune responses. The decreased antibody responses were related not to B cell tolerance but rather to the inability of A␤-specific T cells to provide help for antibody production. The immune hyporesponsiveness could be overcome if T cell help was provided by coupling an A␤ B cell epitope to BSA. Our results suggest that expression of APP in transgenic mice is associated with an A␤-specific impaired adaptive immune response that may contribute to the neuropathology. Moreover, humans with lifelong elevation of brain and peripheral A␤ (e.g., patients with presenilin mutations or Down syndrome) could have reduced immune responses to A␤ vaccination. A lzheimer's disease (AD) is a highly prevalent dementia that is associated with the abnormal accumulation and aggregation of amyloid ␤-peptide (A␤), a process that precedes neuronal injury (reviewed in ref. 1). Accumulating evidence suggests that aggregated forms of A␤ extracellularly, and perhaps also intracellularly, have neurotoxic properties (1-4). Moreover, the autosomal dominant familial forms of AD involve mutations in the genes encoding ␤-amyloid precursor protein (APP), presenilin 1 (PS1), or PS2, and these mutations all cause increased production and accumulation of A␤, a process that begins many years before clinical symptoms (1). A␤ is also overproduced in trisomy 21 (Down syndrome) patients, who overexpress APP from birth, thus making them more susceptible to AD (5, 6). Although there are numerous unresolved issues regarding the molecular and cellular cytotoxic events mediating AD, it is likely that A␤ plays a very early and central role in both the inherited and sporadic forms of the disease.The immune system also appears to participate in AD pathogenesis (7-11). Moreover, immune-based strategies have been shown to be effective in clearing A␤ from the brains of APP transgenic (Tg) mice (12-15). A␤ deposition causes activation of microglia and astrocytes at sites of its accumulation, followed by the induction of an inflammatory response (9,10,16). This inflammatory response may represent in part an attempt by the immune system to clear excess amounts of A␤. The proinflammatory environment in the brain may become chronic probably because of progressive accumulation of A␤ and its aggregation into forms that are less efficiently cleared and͞or more cytotoxic to neurons (7, 10). We hypothesized that chronic exposure of the immune system to A␤ in humans and mouse models might lead to hyporespons...

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Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

Cited by 69 publications

References 46 publications

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Filamentous Tau in Oligodendrocytes and Astrocytes of Transgenic Mice Expressing the Human Tau Isoform with the P301L Mutation

Immune hyporesponsiveness to amyloid β-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease

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Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice

Cited by 69 publications

References 46 publications

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Filamentous Tau in Oligodendrocytes and Astrocytes of Transgenic Mice Expressing the Human Tau Isoform with the P301L Mutation

Immune hyporesponsiveness to amyloid β-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease

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Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model