{"doi":"10.1101/2022.06.07.495164","title":"Excessive Mechanotransduction in Sensory Neurons Causes Joint Contractures in a Mouse Model of Arthrogryposis","abstract":"Abstract Distal arthrogryposis (DA) is a collection of rare disorders characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Remarkably, Botox and a dietary fatty acid that modulates PIEZO2 activity markedly reduce DA5-like deficits. This reveals an unexpected role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":309076,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":560541,"name":"Adrienne E. Dubin","orcid":"0000-0003-4683-7175","position":1,"is_corresponding":false},{"id":298137,"name":"Luis O. Romero","orcid":"0000-0001-9855-7592","position":2,"is_corresponding":false},{"id":560061,"name":"Meaghan Loud","orcid":null,"position":3,"is_corresponding":false},{"id":689502,"name":"Alexandra Salazar","orcid":"0000-0002-6428-9398","position":4,"is_corresponding":false},{"id":1003828,"name":"Yu Wang","orcid":"0000-0002-6074-7048","position":5,"is_corresponding":false},{"id":240292,"name":"Alexander T. Chesler","orcid":"0000-0002-3131-0728","position":6,"is_corresponding":false},{"id":384787,"name":"Katherine Wilkinson","orcid":"0000-0002-2692-5533","position":7,"is_corresponding":false},{"id":298140,"name":"Valeria Vásquez","orcid":"0000-0001-8494-1534","position":8,"is_corresponding":false},{"id":240284,"name":"Kara L. Marshall","orcid":"0000-0003-1722-7941","position":9,"is_corresponding":false},{"id":240293,"name":"Ardem Patapoutian","orcid":"0000-0003-0726-7034","position":10,"is_corresponding":false},{"id":621106,"name":"Shang Ma","orcid":"0000-0003-3808-0651","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T00:33:07.132912Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}