ArticleAnnals of clinical and translational neurology2014
Mice homozygous for c.451C>T mutation in Cln1 gene recapitulate INCL phenotype.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Dysfunction of GABAergic interneurons underlies altered neural network oscillations associated with epileptiform activity in PPT1-deficient mice.Translational psychiatry · 2026Article
- Review
- Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.Acta pharmacologica Sinica · 2025Article
- GABATranslational psychiatry · 2024Article
- Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1.Redox biology · 2024Article
- Crosstalk of Synapsin1 palmitoylation and phosphorylation controls the dynamicity of synaptic vesicles in neurons.Cell death & disease · 2022Article
- Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.International journal of molecular sciences · 2022Review
- Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia.International journal of molecular sciences · 2022Article
- Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.Frontiers in neurology · 2022Review
- GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype.Scientific reports · 2019Article
- Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model.eLife · 2019Article
- Complex StructuralG3 (Bethesda, Md.) · 2019Article
- Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses.Molecular neurodegeneration · 2019Review
- Depalmitoylation by Palmitoyl-Protein Thioesterase 1 in Neuronal Health and Degeneration.Frontiers in synaptic neuroscience · 2019Review
- Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions.Neurobiology of disease · 2017Review
- Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis.Journal of veterinary internal medicine · 2017Article
- Evaluation of disease progression in INCL by MR spectroscopy.Annals of clinical and translational neurology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveNonsense mutations account for 5-70% of all genetic disorders. In the United States, nonsense mutations in the CLN1/PPT1 gene underlie >40% of the patients with infantile neuronal ceroid lipofuscinosis (INCL), a devastating neurodegenerative lysosomal storage disease. We sought to generate a reliable mouse model of INCL carrying the most common Ppt1 nonsense mutation (c.451C>T) found in the United States patient population to provide a platform for evaluating nonsense suppressors in vivo.
methodsWe knocked-in c.451C>T nonsense mutation in the Ppt1 gene in C57 embryonic stem (ES) cells using a targeting vector in which LoxP flanked the Neo cassette, which was removed from targeted ES cells by electroporating Cre. Two independently targeted ES clones were injected into blastocysts to generate syngenic C57 knock-in mice, obviating the necessity for extensive backcrossing.
resultsGeneration of Ppt1-KI mice was confirmed by DNA sequencing, which showed the presence of c.451C>T mutation in the Ppt1 gene. These mice are viable and fertile, although they developed spasticity (a "clasping" phenotype) at a median age of 6 months. Autofluorescent storage materials accumulated throughout the brain regions and in visceral organs. Electron microscopic analysis of the brain and the spleen showed granular osmiophilic deposits. Increased neuronal apoptosis was particularly evident in cerebral cortex and abnormal histopathological and electroretinographic (ERG) analyses attested striking retinal degeneration. Progressive deterioration of motor coordination and behavioral parameters continued until eventual death.
interpretationOur findings show that Ppt1-KI mice reliably recapitulate INCL phenotype providing a platform for testing the efficacy of existing and novel nonsense suppressors in vivo.
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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.