{"doi":"10.1242/dmm.052438","title":"The importance of imperfect pre-clinical models in adolescent idiopathic scoliosis","abstract":"Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, we highlight the current status of pre-clinical models of AIS and discuss the challenges posed by the nature of the disorder combined with the limitations of standard approaches. Current research suggests that straightforward genetic targeting of orthologous AIS disease genes in vertebrates may not necessarily yield equivalent physiological phenotypes but nevertheless can be utilized to understand disease mechanisms. Longer-term, appropriately complex models are needed to fully recapitulate the human AIS phenotype arising from genetic, physiological and mechanical interactions.","journal":"Disease Models & Mechanisms","year":2025,"id":573825,"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":0.9645,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307137,"name":"Ryan S. Gray","orcid":"0000-0001-9668-6497","position":1,"is_corresponding":false},{"id":6730,"name":"Nadav Ahituv","orcid":"0000-0002-7434-8144","position":2,"is_corresponding":false},{"id":247594,"name":"Christina A. Gurnett","orcid":"0000-0001-9129-315X","position":3,"is_corresponding":false},{"id":314823,"name":"Jonathan J. Rios","orcid":"0000-0002-0969-2184","position":4,"is_corresponding":false},{"id":316087,"name":"Lila Solnica‐Krezel","orcid":null,"position":5,"is_corresponding":false},{"id":314819,"name":"Carol A. Wise","orcid":"0000-0002-6790-2194","position":6,"is_corresponding":false},{"id":314820,"name":"Diane S. Sepich","orcid":"0000-0002-1269-9387","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40888060","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":[]}