{"doi":"10.1084/jem.20201879","title":"FGFR3 overactivation in the brain is responsible for memory impairments in Crouzon syndrome mouse model.","abstract":"Crouzon syndrome with acanthosis nigricans (CAN, a rare type of craniosynostosis characterized by premature suture fusion and neurological impairments) has been linked to a gain-of-function mutation (p.Ala391Glu) in fibroblast growth factor receptor 3 (FGFR3). To characterize the CAN mutation's impact on the skull and on brain functions, we developed the first mouse model (Fgfr3A385E/+) of this syndrome. Surprisingly, Fgfr3A385E/+ mice did not exhibit craniosynostosis but did show severe memory impairments, a structurally abnormal hippocampus, low activity-dependent synaptic plasticity, and overactivation of MAPK/ERK and Akt signaling pathways in the hippocampus. Systemic or brain-specific pharmacological inhibition of FGFR3 overactivation by BGJ398 injections rescued the memory impairments observed in Fgfr3A385E/+ mice. The present study is the first to have demonstrated cognitive impairments associated with brain FGFR3 overactivation, independently of skull abnormalities. Our results provide a better understanding of FGFR3's functional role and the impact of its gain-of-function mutation on brain functions. The modulation of FGFR3 signaling might be of value for treating the neurological disorders associated with craniosynostosis.","journal":"PubMed","year":2022,"id":253288,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9478,"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":898735,"name":"Stéphanie Moriceau","orcid":"0000-0002-1413-9359","position":1,"is_corresponding":false},{"id":898736,"name":"Roman Hossein Khonsari","orcid":"0000-0002-0649-1432","position":2,"is_corresponding":false},{"id":898737,"name":"Yann Heuzé","orcid":"0000-0002-0660-9613","position":3,"is_corresponding":false},{"id":755744,"name":"Léa Loisay","orcid":"0000-0002-1988-9458","position":4,"is_corresponding":false},{"id":899233,"name":"Valérie Boitez","orcid":null,"position":5,"is_corresponding":false},{"id":899234,"name":"Anne Morice","orcid":null,"position":6,"is_corresponding":false},{"id":899235,"name":"Eric Arnaud","orcid":null,"position":7,"is_corresponding":false},{"id":896145,"name":"Corinne Collet","orcid":"0000-0001-6990-863X","position":8,"is_corresponding":false},{"id":899236,"name":"Morad Bensidhoum","orcid":null,"position":9,"is_corresponding":false},{"id":746339,"name":"Nabil Kaci","orcid":"0000-0002-6952-6815","position":10,"is_corresponding":false},{"id":899237,"name":"N. Boddaert","orcid":null,"position":11,"is_corresponding":false},{"id":899238,"name":"Giovanna Paternoster","orcid":null,"position":12,"is_corresponding":false},{"id":899239,"name":"Theresa Rauschendorfer","orcid":null,"position":13,"is_corresponding":false},{"id":833793,"name":"Sabine Werner","orcid":"0000-0001-7397-8710","position":14,"is_corresponding":false},{"id":899240,"name":"Suzanne L Mansour","orcid":null,"position":15,"is_corresponding":false},{"id":899241,"name":"Federico Di Rocco","orcid":null,"position":16,"is_corresponding":false},{"id":531452,"name":"Franck Oury","orcid":"0000-0003-0562-9900","position":17,"is_corresponding":false},{"id":348192,"name":"Laurence Legeai‐Mallet","orcid":"0000-0003-4989-5856","position":18,"is_corresponding":false},{"id":898734,"name":"Maxence Cornille","orcid":"0000-0002-8369-1104","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T00:24:55.325369Z","pmid":"35254402","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":[]}