ArticleScientific reports2019
CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease).
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 55 citations in OpenAlex.
- From farm to lab: gene-edited sheep transforming bone research.JBMR plus · 2026Review
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- 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
- Magnetic Resonance Imaging as a Readout of CLN5 Gene Therapy Efficacy in Sheep.Brain and behavior · 2025Article
- Gene editing in livestock: innovations and applications.Animal reproduction · 2024Article
- Recent advances in the genomic resources for sheep.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Sheep as a large animal model for hearing research: comparison to common laboratory animals and humans.Laboratory animal research · 2023Review
- A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes.Disease models & mechanisms · 2023Article
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
- A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.Cerebral circulation - cognition and behavior · 2023Review
- Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis.Brain communications · 2023Article
- Recognising the potential of large animals for modelling neuromuscular junction physiology and disease.Journal of anatomy · 2022Review
- Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.The Journal of clinical investigation · 2022Article
- A Novel Porcine Model of CLN2 Batten Disease that Recapitulates Patient Phenotypes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment.Cells · 2022Review
- Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.International journal of molecular sciences · 2022Review
- Top-down and bottom-up propagation of disease in the neuronal ceroid lipofuscinoses.Frontiers in neurology · 2022Article
- The Translational Benefits of Sheep as Large Animal Models of Human Neurological Disorders.Frontiers in veterinary science · 2022Review
- Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview.Frontiers in neurology · 2022Review
- Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos.Frontiers in genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One of the more severe infantile forms of the disease (INCL or CLN1 disease) is due to mutations in the palmitoyl-protein thioesterase 1 (PPT1) gene and severely reduces the child's lifespan to approximately 9 years of age. In order to better translate the human condition than is possible in mice, we sought to produce a large animal model employing CRISPR/Cas9 gene editing technology. Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus. This resulted in a morphological, anatomical and biochemical disease phenotype that closely resembles the human condition. The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients. Clinical signs included pronounced behavioral deficits as well as motor deficits and complete loss of vision, with a reduced lifespan of 17 ± 1 months at a humanely defined terminal endpoint. Magnetic resonance imaging (MRI) confirmed a significant decrease in motor cortical volume as well as increased ventricular volume corresponding with observed brain atrophy and a profound reduction in brain mass of 30% at necropsy, similar to alterations observed in human patients. In summary, we have generated the first CRISPR/Cas9 gene edited NCL model. This novel sheep model of CLN1 disease develops biochemical, gross morphological and in vivo brain alterations confirming the efficacy of the targeted modification and potential relevance to the human condition.
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.