Expression mapping of tetracycline-responsive prion protein promoter: Digital atlasing for generating cell-specific disease models

Boy, Jana; Leergaard, Trygve B.; Schmidt, Thorsten; Odeh, Francis; Bichelmeier, Ulrike; Nuber, Silke; Holzmann, Carsten; Wree, Andreas; Prusiner, Stanley B.; Bujard, Hermann; Rieß, Olaf; Bjaalie, Jan G.

doi:10.1016/j.neuroimage.2006.05.055

Cited by 26 publications

(48 citation statements)

References 58 publications

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“…Neither qualitative nor quantitative tTA defects can explain the expression patterns displayed by our transgenic lines (supplemental information and data not shown). Therefore, consistent data support the ubiquitous production of tTA and the effective transcriptional activation of tet promoters (Boy et al 2006) when other responder mouse lines are crossed to the same PrP-tTA activator line used in this study. Moreover, the unexpected pattern observed in our mice persisted after changing some responder lines to the FVB/N strain background ( Figure 2B and data not shown).…”

supporting

confidence: 81%

Unexpected Expression Pattern of Tetracycline-Regulated Transgenes in Mice

Bao-Cutrona

Moral

2009

Genetics

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supporting

confidence: 81%

Unexpected Expression Pattern of Tetracycline-Regulated Transgenes in Mice

Bao-Cutrona

Moral

2009

Genetics

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“…A few transgenic strains were then transferred to a FVB/N inbred genetic background. To induce expression of human ATAXIN1 in the brains of transgenic mice, the PrP-tTA (F959 line) (Tremblay et al, 1998) transgenic line was used, which expresses tTA at high levels in all brain regions (Boy et al, 2006).…”

Section: Production and Maintenance Of Tet Transgenic Micementioning

confidence: 99%

“…The transgenic responder line TRE-nSCA74 (transgene copy number 44-56) and the transgenic responder line TRE-eSCA62 (transgene copy number 2-4) were selected because of high levels of ATAXIN1 expression in the CNS when crossed to a CNSspecific tTA-expressing transgenic line (data not shown). These two transgenic lines were then crossed with the PrPtTA transgenic line, which is known to express high levels of tTA mainly in the CNS (Boy et al, 2006).…”

Section: Production and Selection Of Sca1 Tettransgenic Micementioning

confidence: 99%

Reactive astrocytosis and glial glutamate transporter clustering are early changes in a spinocerebellar ataxia type 1 transgenic mouse model

Giovannoni

Maggio²,

Bianco³

et al. 2007

Neuron Glia Biol.

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Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeats within the coding sequence of the ataxin-1 protein. In the present study, we used a conditional transgenic mouse model of SCA1 to investigate very early molecular and morphological changes related to the behavioral phenotype. In mice with neural deficits detected by rotarod performance, and simultaneous spatial impairments in exploratory activity and uncoordinated gait, we observed both significant altered expression and patchy distribution of excitatory amino acids transporter 1. The molecular changes observed in astroglial compartments correlate with changes in synapse morphology; synapses have a dramatic reduction of the synaptic area external to the postsynaptic density. By contrast, Purkinje cells demonstrate preserved structure. In addition, severe reactive astrocytosis matches changes in the glial glutamate transporter and synapse morphology. We propose these morpho-molecular changes are the cause of altered synaptic transmission, which, in turn, determines the onset of the neurological symptoms by altering the synaptic transmission in the cerebellar cortex of transgenic animals. This model might be suitable for testing drugs that target activated glial cells in order to reduce CNS inflammation.Keywords: EAAT1, synaptic plasticity, SCA1, neurodegeneration INTRODUCTIONThe contribution of non-neuronal cells to the pathogenesis of neurodegenerative diseases has been described although the mechanism remains poorly understood. The role of neuron-glia interactions is also being investigated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (Sheldon and Robinson, 2007). Moreover, glial dysfunction is likely to contribute to the pathogenesis of cerebellar ataxia in a mouse model of spinocerebellar ataxia type 7 (SCA7) (Custer et al., 2006).Excitatory amino acids transporter 1 (EAAT1, also known as GLAST) is the major glutamate transporter in the cerebellum (Lehre and Danbolt, 1998). It is expressed strongly by astrocytes in the molecular layer of the cerebellum and is at highest density on Bergmann glia. EAAT1 is not detected in neurons (Ginsberg et al., 1995). EAAT1 present on the plasma membrane of the astrocytic processes and cell bodies (Chaudhry et al., 1995). Targeting of EAAT1 is regulated carefully on astroglial membranes facing the neuropil, large dendrites, cell bodies and capillary endothelium (Danbolt, 2001). Therefore, its distribution follows the morphological changes of astrocytes during inflammatory processes. Recently, in a mouse model of reactive astrocytosis in the spinal cord, it has been reported that this glial process includes a marked proteolytic cascade having as substrates glial transporters. Subsequent changes in neurotransmitter uptake represent the basis of morphological and functional changes that sustain central plasticity . Moreover, glial activation involves changes in cell phenotype and gene expression that might trig...

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“…At the cellular level, CamKII promoter activity is neuron specific and has not been reported in glia (Bukalo et al, 2004;Chen et al, 1998;Mayford et al, 1996Mayford et al, , 1997Michalon et al, 2005;Alvarez-Saavedra et al, 2007), whereas PrP promoter activity is seen in both neuronal and glia cell populations (Boy et al, 2006(Boy et al, , 2009Gotz et al, 2001). Using double-transgenic mice with the LacZ reporter gene (encoding the enzymatically detectable β-galactosidase) as a responder, we have performed comprehensive brain-wide mapping of promoter activity at the level of regions and cells in PrP/ LacZ (Boy et al, 2006) and CamKII/LacZ mice (present study).…”

Section: Introductionmentioning

confidence: 97%

“…CamKII is known as a forebrain specific promoter while the PrP promoter activity is mainly distributed in the brainstem and cerebellum (Bailly et al, 2004;Boy et al, 2006;Bukalo et al, 2004;Chen et al, 1998;Ghavami et al, 1999;Liang et al, 1996;Liu et al, 2001;Mantamadiotis et al, 2002;Mayford et al, 1995Mayford et al, , 1996Tremblay et al, 1998;Alvarez-Saavedra et al, 2007;Yamamoto et al, 2000). At the cellular level, CamKII promoter activity is neuron specific and has not been reported in glia (Bukalo et al, 2004;Chen et al, 1998;Mayford et al, 1996Mayford et al, , 1997Michalon et al, 2005;Alvarez-Saavedra et al, 2007), whereas PrP promoter activity is seen in both neuronal and glia cell populations (Boy et al, 2006(Boy et al, , 2009Gotz et al, 2001). Using double-transgenic mice with the LacZ reporter gene (encoding the enzymatically detectable β-galactosidase) as a responder, we have performed comprehensive brain-wide mapping of promoter activity at the level of regions and cells in PrP/ LacZ (Boy et al, 2006) and CamKII/LacZ mice (present study).…”

Section: Introductionmentioning

confidence: 99%