{"doi":"10.1242/bio.061846","title":"LRRC56 deletion causes primary ciliary dyskinesia in mice characterized by dynein arms defects","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Leucine Rich Repeat Containing protein 56 (LRRC56), also known as DNAAF12, is a member of the LRRC superfamily, whose dysfunction is associated with mucociliary clearance and laterality defects in humans. Here, we generated LRRC56-knockout mice using the CRISPR/Cas9 nuclease system to specifically target exons 4-5 of the LRRC56 gene. We observed that homozygous LRRC56 gene deletion is definitely deleterious, as 27.8% of LRRC56−/− mice died before adulthood. Among the surviving LRRC56−/− mice, the most prominent phenotypes included hydrocephalus, situs inversus, male infertility, and bronchiectasis. Transmission electron microscopy revealed defects in dynein arms of cilia and disorganized axonemal structure in flagella. Immunofluorescence analysis similarly revealed the absence of inner and outer dynein arm markers DNALI1 and DNAI2 in the cilia. Heterozygous LRRC56+/− mice developed normally, without exhibiting any symptoms of primary ciliary dyskinesia. In conclusion, the knockout of the LRRC56 gene in mice leads to a range of conditions consistent with primary ciliary dyskinesia. The absence of DNALI1 and DNAI2 signaling in knockout mouse cilia supports the critical role of the LRRC56 gene in dynein arm assembly.</jats:p>","journal":"Biology Open","year":2025,"id":611426,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1573559,"name":"Huilong Li","orcid":null,"position":1,"is_corresponding":false},{"id":1573560,"name":"Pingyun Wu","orcid":null,"position":2,"is_corresponding":false},{"id":1323407,"name":"Qi Yang","orcid":"0000-0001-9607-9881","position":3,"is_corresponding":false},{"id":1573561,"name":"Xueting Wan","orcid":null,"position":4,"is_corresponding":false},{"id":1016060,"name":"Yuan Wu","orcid":"0000-0003-2262-9494","position":5,"is_corresponding":false},{"id":1573558,"name":"Ruolan Wu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"LRRC56 deletion causes primary ciliary dyskinesia in mice characterized by dynein arms defects","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Leucine Rich Repeat Containing protein 56 (LRRC56), also known as DNAAF12, is a member of the LRRC superfamily, whose dysfunction is associated with mucociliary clearance and laterality defects in humans. Here, we generated LRRC56-knockout mice using the CRISPR/Cas9 nuclease system to specifically target exons 4-5 of the LRRC56 gene. We observed that homozygous LRRC56 gene deletion is definitely deleterious, as 27.8% of LRRC56−/− mice died before adulthood. Among the surviving LRRC56−/− mice, the most prominent phenotypes included hydrocephalus, situs inversus, male infertility, and bronchiectasis. Transmission electron microscopy revealed defects in dynein arms of cilia and disorganized axonemal structure in flagella. Immunofluorescence analysis similarly revealed the absence of inner and outer dynein arm markers DNALI1 and DNAI2 in the cilia. Heterozygous LRRC56+/− mice developed normally, without exhibiting any symptoms of primary ciliary dyskinesia. In conclusion, the knockout of the LRRC56 gene in mice leads to a range of conditions consistent with primary ciliary dyskinesia. The absence of DNALI1 and DNAI2 signaling in knockout mouse cilia supports the critical role of the LRRC56 gene in dynein arm assembly.</jats:p>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39912490","pmcid":"PMC11832119","openalex_id":"https://openalex.org/W4407190509","authors":[],"funders":[{"funder_name":"National Natural Science Foundation","grant_id":"82002238","title":null},{"funder_name":"Central South University Third Xiangya Hospital","grant_id":"","title":null}],"total_grants":2,"fwci":5.2608,"citation_percentile":0.95610542,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1242/bio.061846","host_type":"journal"},{"url":"https://doi.org/10.1242/bio.061846","host_type":"publisher"},{"url":"https://journals.biologists.com/bio/article-pdf/doi/10.1242/bio.061846/3617104/bio061846.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39912490","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11832119","host_type":"repository"},{"url":"https://doaj.org/article/37eddba3979447e398562e7c2264c6c7","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11832119","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11832119?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cystic Fibrosis Research Advances","Genetic and Kidney Cyst Diseases","Genomic variations and chromosomal abnormalities"],"mesh_terms":["Animals","Cilia","Ciliary Motility Disorders","Disease Models, Animal","Dyneins","Kartagener Syndrome","Male","Membrane Proteins","Phenotype","Gene Deletion","Mice, Knockout","Mice","CRISPR-Cas Systems"],"keywords":["Primary ciliary dyskinesia","Cilium","Dynein","Biology","Intraflagellar transport","Situs inversus","Knockout mouse","Gene knockout","Axoneme","Dynein ATPase","Motile cilium","Flagellum","Genetics","Cell biology","Exon","Gene","Microtubule","Bronchiectasis","Anatomy","Internal medicine","Medicine","Male infertility","Hydrocephalus","Lrrc56"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T19:26:47.455712Z","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":[]}