ArticleHuman molecular genetics2015
The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- TREM2-Mediated Cholesterol Efflux in Macrophages Inhibits Anti-Tumor Immunity via Limitation of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AAV-delivered PPT1 provides long-term neurological benefits in CLN1 mice and achieves therapeutic levels in sheep brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
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- Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.Acta pharmacologica Sinica · 2025Article
- Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Identification of New Modulators and Inhibitors of Palmitoyl-Protein Thioesterase 1 for CLN1 Batten Disease and Cancer.ACS omega · 2024Article
- Readthrough Activators and Nonsense-Mediated mRNA Decay Inhibitor Molecules: Real Potential in Many Genetic Diseases Harboring Premature Termination Codons.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Acidified drinking water attenuates motor deficits and brain pathology in a mouse model of a childhood neurodegenerative disorder.Scientific reports · 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
- Glycerophosphoinositol is Elevated in Blood Samples FromBiomarker insights · 2022Article
- Slivers of the spectrum.Nature biotechnology · 2021Article
- Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death.PloS one · 2021Article
- Comparative analysis of the gut microbiota composition in the Cln1Archives of microbiology · 2021Article
- A tailored Cln3Scientific reports · 2020Article
- RNA-based therapies in animal models of Leber congenital amaurosis causing blindness.Precision clinical medicine · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive neurodegenerative disorders in children characterized by the progressive onset of seizures, blindness, motor and cognitive decline and premature death. Patients with mutations in CLN1 primarily manifest with infantile NCL (INCL or Haltia-Santavuori disease), which is second only to congenital NCL for its age of onset and devastating progression. CLN1 encodes a lysosomal enzyme, palmitoyl-protein thioesterase 1 (PPT1). Nonsense mutations in CLN1 account for 52.3% of all disease causing alleles in infantile NCL, the most common of which worldwide is the p.R151X mutation. Previously, we have shown how nonsense-mediated decay is involved in the degradation of CLN1 mRNA transcripts containing the p.R151X mutation in human lymphoblast cell lines. We have also shown how the read-through drugs gentamicin and ataluren (PTC124) increase CLN1 (PPT1) enzyme activity. Here, we provide the initial characterization of the novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis that we have generated. This nonsense mutation model recapitulates the molecular, histological and behavioral phenotypes of the human disease. Cln1(R151X) mice showed a significant decrease in Cln1 mRNA level and PPT1 enzyme activity, accumulation of autofluorescent storage material, astrocytosis and microglial activation in the brain. Behavioral characterization of Cln1(R151X) mice at 3 and 5 months of age revealed significant motor deficits as measured by the vertical pole and rotarod tests. We also show how the read-through compound ataluren (PTC124) increases PPT1 enzyme activity and protein level in Cln1(R151X) mice in a proof-of-principle study.
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