ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 149 citations in OpenAlex.
- Pathological gain-of-function human variants in the GRIK2 kainate receptor gene cause wide-ranging behavioral dysfunction and seizures in mouse models.Neurobiology of disease · 2026Article
- Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis.Molecular therapy. Methods & clinical development · 2025Article
- Autonomous STING signaling in Purkinje cells drives neurodegeneration independent of type I interferon.Cell reports · 2025Article
- Assessment of motor deterioration in a cynomolgus macaque with neuronal ceroid lipofuscinosis type 2 disease using two behavioral analyses.The Journal of veterinary medical science · 2025Article
- GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.JCI insight · 2025Article
- Recreating pathophysiology of CLN2 disease and demonstrating reversion by TPP1 gene therapy in hiPSC-derived retinal organoids and retina-on-chip.Cell reports. Medicine · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- The involvement of Purkinje cells in progressive myoclonic epilepsy: Focus on neuronal ceroid lipofuscinosis.Neurobiology of disease · 2023Review
- A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.Journal of inherited metabolic disease · 2023Article
- Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model.The Journal of clinical investigation · 2023Article
- Article
- Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model.Scientific reports · 2023Article
- Neonatal lethality of mouse A/J-7Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders.Cell death and differentiation · 2022Article
- A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.International journal of molecular sciences · 2022Review
- Limited astrocyte-to-neuron conversion in the mouse brain using NeuroD1 overexpression.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression.Journal of neuroinflammation · 2021Article
- Exploiting the diphtheria toxin internalization receptor enhances delivery of proteins to lysosomes for enzyme replacement therapy.Science advances · 2020Article
- A tailored Cln3Scientific reports · 2020Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in the CLN2 gene, which encodes a lysosomal serine protease, tripeptidyl-peptidase I (TPP I), result in an autosomal recessive neurodegenerative disease of children, classical late-infantile neuronal ceroid lipofuscinosis (cLINCL). cLINCL is inevitably fatal, and there currently exists no cure or effective treatment. In this report, we provide the characterization of the first CLN2-targeted mouse model for cLINCL. CLN2-targeted mice were fertile and apparently healthy at birth despite an absence of detectable TPP I activity. At approximately 7 weeks of age, neurological deficiencies became evident with the onset of a tremor that became progressively more severe and was eventually accompanied by ataxia. Lifespan of the affected mice was greatly reduced (median survival, 138 d), and extensive neuronal pathology was observed including a prominent accumulation of cytoplasmic storage material within the lysosomal-endosomal compartment, a loss of cerebellar Purkinje cells, and widespread axonal degeneration. The CLN2-targeted mouse therefore recapitulates much of the pathology and clinical features of cLINCL and represents an animal model that should provide clues to the normal cellular function of TPP I and the pathogenic processes that underlie neuronal death in its absence. In addition, the CLN2-targeted mouse also represents a valuable model for the evaluation of different therapeutic strategies.
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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.