Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice

Hirrlinger, Petra G.; Scheller, Anja; Braun, Christian; Quintela-Schneider, Markus; Fuss, Babette; Hirrlinger, Johannes; Kirchhoff, Frank

doi:10.1016/j.mcn.2005.08.011

Cited by 155 publications

(136 citation statements)

References 42 publications

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“…21 Other promoters are either not neuron-specific such as the platelet-derived growth factor (PDGF) promoter or weak such as the CaMK-II (Ca 2ϩ -calmodulin-dependent kinase II) promoter. The main criticism of the Thy1.2 promoter is its strong efficiency in motor neurons.…”

Section: Discussionmentioning

confidence: 99%

“…This cDNA-construct was inserted into the XhoI-sites of a Thy1.2 expression vector. 19,20 The Thy1.2 promotor specifically drives expression in neurons 19 that starts at postnatal day 6 21 and therefore does not directly affect embryonic development. The vector was then microinjected into a C57BL6/CBA background and backcrossed to C57BL6 for more than five generations.…”

Section: Generation Of Tg Mice Expressing G272v and P301s Human Taumentioning

confidence: 99%

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Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits

Schindowski

Bretteville

Leroy³

et al. 2006

The American Journal of Pathology

331

377

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Tau transgenic mice are valuable models to investigate the role of tau protein in Alzheimer's disease and other tauopathies. However, motor dysfunction and dystonic posture interfering with behavioral testing are the most common undesirable effects of tau transgenic mice. Therefore, we have generated a novel mouse model (THY-Tau22) that expresses human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2-promotor, displaying tau pathology in the absence of any motor dysfunction. THY-Tau22 shows hyperphosphorylation of tau on several Alzheimer's disease-relevant tau epitopes (AT8, AT100, AT180, AT270, 12E8, taupSer396, and AP422), neurofibrillary tangle-like inclusions (Gallyas and MC1-positive) with rare ghost tangles and PHF-like filaments, as well as mild astrogliosis. These mice also display deficits in hippocampal synaptic transmission and impaired behavior characterized by increased anxiety, delayed learning from 3 months, and reduced spatial memory at 10 months. There are no signs of motor deficits or changes in motor activity at any age investigated. This mouse model therefore displays the main features of tau pathology and several of the pathophysiological disturbances observed during neurofibrillary degeneration. This model will serve as an experimental tool in future studies to investigate mechanisms underlying cognitive deficits during pathogenic tau aggregation. Alzheimer's disease (AD) is the most common form of dementia in the elderly and is characterized neuropathologically by the presence of intracellular neurofibrillary tangles (NFTs) and senile plaques in the brain and by a major loss of synaptic connections. NFTs are neuronal inclusions of the microtubule-associated tau protein and are composed of aggregated phosphorylated tau. In AD, NFTs occur in the hippocampus, the entorhinal and polymodal association cortices, and in the basal forebrain. These brain areas are also severely affected by neuronal and synaptic loss. The loss of neurites, synapses, and neurons represent one of the reasons for the cognitive deficits and dementia of AD.

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Section: Discussionmentioning

confidence: 99%

Section: Generation Of Tg Mice Expressing G272v and P301s Human Taumentioning

confidence: 99%

Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits

Schindowski

Bretteville

Leroy³

et al. 2006

The American Journal of Pathology

331

377

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“…Heterozygous Olig2::CreER TM (Takebayashi et al, 2002) were crossed with the PLP-dsRed (Hirrlinger et al, 2005) or the reporter mice Z/EG (Novak et al, 2000) or R26R (Soriano, 1999) to obtain doubleheterozygous animals. Double-heterozygous mice older than 2.5 months received tamoxifen orally (10 mg; dissolved at 40 mg/ml in a 1:9 ethanol/ corn oil mixture) three times (once a day every second day for 5 d).…”

Section: Methodsmentioning

confidence: 99%

“…Toward this end, we crossed the Olig2::CreER TM ;Z/EG mice to PLP-dsRed animals (Hirrlinger et al, 2005), visualizing the expression from a myelin protein promoter by cytoplasmic localization of fluorescent protein (supplemental Fig. 5A-C, available at www.jneurosci.org as supplemental material).…”

Section: Cells Labeled Bymentioning

confidence: 99%

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Dimou¹,

Simon²,

Kirchhoff³

et al. 2008

J. Neurosci.

482

564

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Despite their abundance, still little is known about the rather frequent, constantly proliferating progenitors spread throughout the adult mouse brain parenchyma. The majority of these progenitors express the basic-helix-loop-helix transcription factor Olig2, and their number further increases after injury. Here, we examine the progeny of this progenitor population by genetic fate mapping using tamoxifen-inducible Cre-recombination in the Olig2 locus to turn on permanent reporter gene expression in the adult brain. Consistent with Olig2 expression in proliferating NG2 ϩ progenitors, most reporter ϩ cells seen shortly after initiating recombination at adult stages incorporated BrdU and contained the proteoglycan NG2 in both the gray (GM) and the white matter (WM) of the cerebral cortex. However, at longer time points after induction, we observed profound differences in the identity of reporter ϩ cells in the WM and GM. Whereas most of the Olig2 ϩ progenitors had generated mature, myelinating oligodendrocytes in the WM, hardly any reporter ϩ cells showing mature oligodendrocyte characteristics were detectable even up to 6 months after recombination in the GM. In the GM, most reporter ϩ cells remained NG2 ϩ , even after injury, but stopped proliferating rather soon after recombination. Thus, our results demonstrate the continuous generation of mature, myelinating oligodendrocytes in the WM, whereas cells in the GM generated mostly postmitotic NG2 ϩ glia.

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“…In some cases this has been reported to interfere with proper intracellular localization of fusion constructs or to compromise cellular structures such as the actin or tubulin cytoskeleton 13,14 . We observed no mislocalization or aggregation in this study.…”

mentioning

confidence: 99%

An improved mRFP1 adds red to bimolecular fluorescence complementation

et al. 2006

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Protein-protein interactions are fundamental to virtually every aspect of cellular functions. Blue, green and yellow bimolecular fluorescence complementation (BiFC) systems based on GFP and its variants allow the investigation of protein-protein interactions in vivo. We have developed the first red BiFC system based on an improved monomeric red fluorescent protein (mRFP1-Q66T), expanding the range of possible applications for BiFC.With interactome data available for several model organisms, a challenging next step in post-genomic research is to analyze protein complex formation in vivo. The recently developed BiFC assay is a comparably fast and simple noninvasive technology to study protein interactions inside living cells. BiFC is based on the reconstitution of the yellow fluorescent protein (YFP) from two nonfluorescent fragments when they are brought into close proximity by a physical interaction between proteins fused to each fragment 1 . This approach has proven to be robust and versatile, and multicolor versions using spectral variants of GFP further increase the potential of this technology 2 . The color spectrum available for BiFC, however, has been limited to blue, green and yellow.The red fluorescent protein from Discosoma sp. (DsRED) and its variants are established intracellular reporter proteins, but the characteristics of most DsRED variants, particularly their obligate tetramerization, impede their application in BiFC 3,4 . An extensively mutated monomeric DsRED variant (mRFP1) has been generated 5 , but substantially altered spectra, poor brightness and low photostability limit its usefulness as a reporter protein.We have identified improved mRFP1 mutants, which allowed us to establish a red fluorescent reporter system for detection of protein interactions in vivo. We used site-directed mutagenesis to generate mRFP1 variants with a randomized first position of the fluorophore. Screening of 5,000 colonies resulted in the identification of 50 clones exhibiting strong red fluorescence representing three different mutations (Q66C, Q66S and Q66T) with frequencies of 5%, 43% and 52%, respectively.

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Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice

Cited by 155 publications

References 42 publications

Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits

Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor Deficits

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

An improved mRFP1 adds red to bimolecular fluorescence complementation

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