ArticleScientific reports2018
Genetic engineering a large animal model of human hypophosphatasia in sheep.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- From farm to lab: gene-edited sheep transforming bone research.JBMR plus · 2026Review
- Efzimfotase Alfa Improves Respiratory Capacity in Muscle Tissue From a Mouse Model of HPP.JIMD reports · 2026Article
- Modeling and prediction of body segment inertial properties of sheep from tomographic imaging.Journal of biomechanics · 2025Article
- Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval.Advances in therapy · 2025Review
- Predictive estimation of ovine hip joint centers: Neural networks vs. linear regression.Journal of biomechanics · 2025Article
- Review
- Establishment of human periodontal ligament cell lines withFrontiers in cell and developmental biology · 2025Article
- Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.Journal of the American Dental Association (1939) · 2024Review
- Opportunities for CRISPR-Cas9 application in farm animal genetic improvement.Molecular biology reports · 2024Review
- Genome editing: An insight into disease resistance, production efficiency, and biomedical applications in livestock.Functional & integrative genomics · 2024Review
- Compromised Muscle Properties in a Severe Hypophosphatasia Murine Model.International journal of molecular sciences · 2023Article
- The Past, Present, and Future of Genetically Engineered Mouse Models for Skeletal Biology.Biomolecules · 2023Review
- Perspectives in Genome-Editing Techniques for Livestock.Animals : an open access journal from MDPI · 2023Review
- Review
- Dentoalveolar Defects of Hypophosphatasia are Recapitulated in a Sheep Knock-In Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The Sheep as a Large Animal Model for the Investigation and Treatment of Human Disorders.Biology · 2022Review
- Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?Frontiers in dental medicine · 2022Article
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Application of CRISPR/Cas9 System in Establishing Large Animal Models.Frontiers in cell and developmental biology · 2022Review
- Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm.Cells · 2021Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The availability of tools to accurately replicate the clinical phenotype of rare human diseases is a key step toward improved understanding of disease progression and the development of more effective therapeutics. We successfully generated the first large animal model of a rare human bone disease, hypophosphatasia (HPP) using CRISPR/Cas9 to introduce a single point mutation in the tissue nonspecific alkaline phosphatase (TNSALP) gene (ALPL) (1077 C > G) in sheep. HPP is a rare inherited disorder of mineral metabolism that affects bone and tooth development, and is associated with muscle weakness. Compared to wild-type (WT) controls, HPP sheep have reduced serum alkaline phosphatase activity, decreased tail vertebral bone size, and metaphyseal flaring, consistent with the mineralization deficits observed in human HPP patients. Computed tomography revealed short roots and thin dentin in incisors, and reduced mandibular bone in HPP vs. WT sheep, accurately replicating odonto-HPP. Skeletal muscle biopsies revealed aberrant fiber size and disorganized mitochondrial cristae structure in HPP vs. WT sheep. These genetically engineered sheep accurately phenocopy human HPP and provide a novel large animal platform for the longitudinal study of HPP progression, as well as other rare human bone diseases.
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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.