ArticleHuman molecular genetics2011
P0S63del impedes the arrival of wild-type P0 glycoprotein to myelin in CMT1B mice.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- A novel mouse model of CMT1B identifies hyperglycosylation as a new pathogenetic mechanism.Human molecular genetics · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.Human molecular genetics · 2019Article
- Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B.Annals of clinical and translational neurology · 2018Article
- Article
- Ablation of Perk in Schwann Cells Improves Myelination in the S63del Charcot-Marie-Tooth 1B Mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Endoplasmic Reticulum Protein Quality Control Failure in Myelin Disorders.Frontiers in molecular neuroscience · 2016Review
- HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins.PLoS biology · 2015Article
- CFTR-deficient pigs display peripheral nervous system defects at birth.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
More than 120 mutations in the Myelin Protein Zero gene (MPZ, P0) cause various forms of hereditary neuropathy. Two human mutations encoding either P0S63C or P0S63del have been shown to cause demyelination in mice through different gain of function pathomechanisms. P0S63del, for example, is retained in the endoplasmic reticulum (ER) and elicits a pathogenetic unfolded protein response (UPR). As P0 likely forms oligomers, another gain of abnormal function could include a dominant-negative interaction between P0S63del and normal P0 (P0wt). To test this idea, we generated a transgenic mouse that expressed a form of P0wt with a myc epitope tag at the C terminus (P0ct-myc). We show that P0ct-myc is trafficked and functions like P0wt, thus providing a new tool to study P0 in vivo. In mice that express both P0ct-myc and P0S63del, P0S63del specifically delays the transit of P0ct-myc through the ER and reduces the level of P0wt in the myelin sheath by half-a level previously shown to cause demyelination in mice and humans. Surprisingly, P0ct-myc does not co-immunoprecipitate with P0S63del, suggesting an indirect interaction. Thus, P0S63del causes not only a UPR-related toxic mechanism, but also a dominant-negative effect on P0wt that probably contributes to demyelinating neuropathy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.