Genome-Edited Coincidence and PMP22-HiBiT Fusion Reporter Cell Lines Enable an Artifact-Suppressive Quantitative High-Throughput Screening Strategy for PMP22 Gene-Dosage Disorder Drug Discovery
نویسندگان
چکیده
منابع مشابه
Genetic dosage compensation via co-occurrence of PMP22 duplication and PMP22 deletion.
Charcot-Marie-Tooth disease type 1 A (CMT1A, OMIM #118220) and hereditary neuropathy with liability to pressure palsies (HNPP or tomaculous neu-ropathy, OMIM #162500) are autosomal dominantly inherited neuropathies caused by genomic rearrangements on chromosome 17p11.2-p12 containing PMP22. Heterozygous PMP22 duplications result in a peripheral neuropathy characterized by distal muscular atroph...
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Drug screening is a long and costly process confronted with low productivity and challenges in using animals, which limit the discovery of new drugs. To improve drug screening efficacy and minimize animal testing, recent efforts have been dedicated to developing cell-based high throughput screening (HTS) platforms that can provide more relevant in vivo biological information than biochemical as...
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Copy number variation resulting in excess PMP22 protein causes the peripheral neuropathy Charcot-Marie-Tooth disease, type 1A. To broadly interrogate chemically sensitive transcriptional pathways controlling PMP22 protein levels, we used the targeting precision of TALEN-mediated genome editing to embed reporters within the genetic locus harboring the Peripheral Myelin Protein 22 (Pmp22) gene. U...
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متن کاملDiagnosis of gene dosage alterations at the PMP22 gene using MAPH.
G enomic rearrangements due to submicroscopic duplications or deletions are responsible for many inherited disorders, and a gene (or genes) sensitive to dosage alterations may be involved in these structural rearrangements. The segment involved is generally smaller than 2 Mb and cannot be detected by conventional karyotyping. Charcot-Marie-Tooth disease type 1A (CMT1A) [OMIM #118220] and heredi...
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ژورنال
عنوان ژورنال: ACS Pharmacology & Translational Science
سال: 2021
ISSN: 2575-9108,2575-9108
DOI: 10.1021/acsptsci.1c00110