ArticlePloS one2011
Expression and in vivo rescue of human ABCC6 disease-causing mutants in mouse liver.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 72 citations in OpenAlex.
- Three People With Recurrent Nephrolithiasis and HeterozygousKidney medicine · 2026Article
- Multi-State Structural Genomics Enables Large-Scale, Mechanistic, and Context-Specific Classification of ABCC6 Genetic Variants Implicated in Calcification Diseases.International journal of molecular sciences · 2026Article
- The Purinergic Nature of Pseudoxanthoma Elasticum.Biology · 2024Review
- Mitochondrial Dysfunction and Oxidative Stress in Hereditary Ectopic Calcification Diseases.International journal of molecular sciences · 2022Review
- ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.Human mutation · 2022Review
- The pathogenic c.1171A>G (p.Arg391Gly) and c.2359G>A (p.Val787Ile) ABCC6 variants display incomplete penetrance causing pseudoxanthoma elasticum in a subset of individuals.Human mutation · 2022Article
- Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Functional Assessment of Missense Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.The Journal of investigative dermatology · 2022Article
- ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification.PLoS genetics · 2022Article
- Review
- Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.The Journal of investigative dermatology · 2021Review
- ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions.International journal of molecular sciences · 2021Review
- Reassessment of causality of ABCC6 missense variants associated with pseudoxanthoma elasticum based on Sherloc.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Therapeutics Development for Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders: Update 2020.Journal of clinical medicine · 2020Review
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients.The Journal of investigative dermatology · 2019Article
- PXE, a Mysterious Inborn Error Clarified.Trends in biochemical sciences · 2019Review
- Persistence of the ABCC6 genes and the emergence of the bony skeleton in vertebrates.Scientific reports · 2018Article
- Tissue-nonspecific alkaline phosphatase: a promising target for pseudoxanthoma elasticum therapy.Annals of translational medicine · 2017Article
- The ABCC6 Transporter: A New Player in Biomineralization.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss-of-function mutations in ABCC6 can cause chronic or acute forms of dystrophic mineralization described in disease models such as pseudoxanthoma elasticum (OMIM 26480) in human and dystrophic cardiac calcification in mice. The ABCC6 protein is a large membrane-embedded organic anion transporter primarily found in the plasma membrane of hepatocytes. We have established a complex experimental strategy to determine the structural and functional consequences of disease-causing mutations in the human ABCC6. The major aim of our study was to identify mutants with preserved transport activity but failure in intracellular targeting. Five missense mutations were investigated: R1138Q, V1298F, R1314W, G1321S and R1339C. Using in vitro assays, we have identified two variants; R1138Q and R1314W that retained significant transport activity. All mutants were transiently expressed in vivo, in mouse liver via hydrodynamic tail vein injections. The inactive V1298F was the only mutant that showed normal cellular localization in liver hepatocytes while the other mutants showed mostly intracellular accumulation indicating abnormal trafficking. As both R1138Q and R1314W displayed endoplasmic reticulum localization, we tested whether 4-phenylbutyrate (4-PBA), a drug approved for clinical use, could restore their intracellular trafficking to the plasma membrane in MDCKII and mouse liver. The cellular localization of R1314W was significantly improved by 4-PBA treatment, thus potentially rescuing its physiological function. Our work demonstrates the feasibility of the in vivo rescue of cellular maturation of some ABCC6 mutants in physiological conditions very similar to the biology of the fully differentiated human liver and could have future human therapeutic application.
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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.