Neuropathology in Mice Expressing Human α-Synuclein

Putten, Herman van der; Wiederhold, Karl‐Heinz; Probst, A.; Barbieri, Samuel; Mistl, Claudia; Danner, Simone; Kauffmann, Serge; Hofele, Katja; Spooren, Will; Rüegg, Markus A.; Lin, Shuo; Caroni, Pico; Sommer, Bernd; Tolnay, Markus; Bilbe, Graeme

doi:10.1523/jneurosci.20-16-06021.2000

Cited by 483 publications

(338 citation statements)

References 53 publications

(115 reference statements)

Supporting

Mentioning

300

Contrasting

Unclassified

Order By: Relevance

“…The exact disposition of 'perisynaptic fibroblasts' is unclear from previous reports, since they were depicted diagrammatically to be near to, but not overlying, neuromuscular junctions (Murray and Robbins, 1982;Gatchalian et al, 1989;Weis et al, 1991). No discernible immunofluorescence of NMJ-capping cells was detected using Thy-1 antibody, although axons, which also express Thy-1 antigen were immunolabelled (Reynolds and Woolf, 1992;Feng et al, 2000;Van der Putten et al, 2000). There were other Thy-1-positive cells near the NMJ but these did not include the 2166-positive NMJ-capping cells (supplementary material Fig.…”

Section: Nmj-capping Cells Show a Distinct Immunocytochemical Profilementioning

confidence: 86%

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Court

Gillingwater

Melrose

et al. 2008

Journal of Cell Science

View full text Add to dashboard Cite

Neuromuscular junctions (NMJs) are normally thought to comprise three major cell types: skeletal muscle fibres, motor neuron terminals and perisynaptic terminal Schwann cells. Here we studied a fourth population of junctional cells in mice and rats, revealed using a novel cytoskeletal antibody (2166). These cells lie outside the synaptic basal lamina but form caps over NMJs during postnatal development. NMJ-capping cells also bound rPH, HM-24, CD34 antibodies and cholera toxin B subunit. Bromodeoxyuridine incorporation indicated activation, proliferation and spread of NMJ-capping cells following denervation in adults, in advance of terminal Schwann cell sprouting. The NMJ-capping cell reaction coincided with expression of tenascin-C but was independent of this molecule because capping cells also dispersed after denervation in tenascin-C-null mutant mice. NMJ-capping cells also dispersed after local paralysis with botulinum toxin and in atrophic muscles of transgenic R6/2 mice. We conclude that NMJ-capping cells (proposed name `kranocytes') represent a neglected, canonical cellular constituent of neuromuscular junctions where they could play a permissive role in synaptic regeneration.

show abstract

Section: Nmj-capping Cells Show a Distinct Immunocytochemical Profilementioning

confidence: 86%

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Court

Gillingwater

Melrose

et al. 2008

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In vitro, the phosphorylation of serine-129 has been shown to promote fibril formation, a particular form of aggregation, and often thought to be associated with disease . All mouse models of overexpressed a-synuclein (Masliah et al 2000;van der Putten et al 2000) and in vitro studies with wild-type and early-onset Parkinson's disease mutant a-synuclein produce non-fibrillar oligomers (Conway et al 2000). However, the Drosophila model of a-synuclein did produce fibrils (Feany and Bender 2000).…”

Section: Discussionmentioning

confidence: 99%

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Papay

Zuscik

Ross

et al. 2002

Journal of Neurochemistry

View full text Add to dashboard Cite

We had previously reported that systemic overexpression of the a 1B -adrenergic receptor (AR) in a transgenic mouse induced a neurodegenerative disease that resembled the parkinsonian-like syndrome called multiple system atrophy (MSA). We now report that our mouse model has cytoplasmic inclusion bodies that colocalize with oligodendrocytes and neurons, are positive for a-synuclein and ubiquitin, and therefore may be classified as a synucleinopathy. a-Synuclein monomers as well as multimers were present in brain extracts from both normal and transgenic mice. However, similar to human MSA and other synucleinopathies, transgenic mice showed an increase in abnormal aggregated forms of a-synuclein, which also increased its nitrated content with age.However, the same extracts displayed decreased phosphorylation of a-synuclein. Other traits particular to MSA such as Purkinje cell loss in the cerebellum and degeneration of the intermediolateral cell columns of the spinal cord also exist in our mouse model but differences still exist between them. Interestingly, long-term therapy with the a 1 -AR antagonist, terazosin, resulted in protection against the symptomatic as well as the neurodegeneration and a-synuclein inclusion body formation, suggesting that signaling of the a 1B -AR is the cause of the pathology. We conclude that overexpression of the a 1B -AR can cause a synucleinopathy similar to other parkinsonian syndromes.

show abstract

“…The Murine Thy-1 Promoter Importantly, in contrast to other lines of mice using the Thy-1 promoter [25], the Thy1-aSyn mice of line 61 do not exhibit obvious motor neuron pathology [21] and do not show motor neuron deficits in behavioral tests [26]. The absence of motor neuron degeneration in Thy1-aSyn mice is critically important, as their behavioral deficits are more likely to reflect impairments that are relevant to PD and single out the Thy1-aSyn mice as particularly suitable for preclinical drug testing, described as follows.…”

Section: Genetic Background and Transgene Insertionmentioning

confidence: 99%

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

et al. 2012

View full text Add to dashboard Cite

Identification of mutations that cause rare familial forms of Parkinson's disease (PD) and subsequent studies of genetic risk factors for sporadic PD have led to an improved understanding of the pathological mechanisms that may cause nonfamilial PD. In particular, genetic and pathological studies strongly suggest that alpha-synuclein, albeit very rarely mutated in PD patients, plays a critical role in the vast majority of individuals with the sporadic form of the disease. We have extensively characterized a mouse model over-expressing full-length, human, wild-type alpha-synuclein under the Thy-1 promoter. We have also shown that this model reproduces many features of sporadic PD, including progressive changes in dopamine release and striatal content, alphasynuclein pathology, deficits in motor and nonmotor functions that are affected in pre-manifest and manifest phases of PD, inflammation, and biochemical and molecular changes similar to those observed in PD. Preclinical studies have already demonstrated improvement with promising new drugs in this model, which provides an opportunity to test novel neuroprotective strategies during different phases of the disorder using endpoint measures with high power to detect drug effects.

show abstract

Neuropathology in Mice Expressing Human α-Synuclein

Cited by 483 publications

References 53 publications

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

Contact Info

Product

Resources

About

Neuropathology in Mice Expressing Human α-Synuclein

Cited by 483 publications

References 53 publications

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Mice expressing the α1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

Contact Info

Product

Resources

About

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation