{"doi":"10.1242/dev.201593","title":"<i>Actl7b</i>\n                    deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>Actin-related proteins (Arps) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp, and is highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b−/−) were infertile, whereas heterozygous males (Actl7b+/−) were fertile. Severe spermatid defects, such as detached acrosomes, disrupted membranes and flagella malformations start to appear after spermiogenesis step 9 in Actl7b−/− mice, finally resulting in spermatogenic arrest. Abnormal spermatids were degraded and levels of autophagy markers were increased. Co-immunoprecipitation with mass spectrometry experiments identified an interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establish that mutations in ACTL7B are directly related to male infertility, pressing for additional research in humans.</jats:p>","journal":"Development","year":2023,"id":621340,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"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":1080782,"name":"Lena Arévalo","orcid":"0000-0002-0681-0392","position":1,"is_corresponding":false},{"id":1604306,"name":"Andjela Kovacevic","orcid":"0000-0001-7719-2467","position":2,"is_corresponding":false},{"id":446550,"name":"Keerthika Lohanadan","orcid":null,"position":3,"is_corresponding":false},{"id":357010,"name":"Dirk G. de Rooij","orcid":"0000-0003-3932-4419","position":4,"is_corresponding":false},{"id":1604307,"name":"Carla Simon","orcid":"0009-0009-9687-3730","position":5,"is_corresponding":false},{"id":1604309,"name":"Melanie Jokwitz","orcid":null,"position":6,"is_corresponding":false},{"id":1604311,"name":"Walter Witke","orcid":"0000-0001-5018-0060","position":7,"is_corresponding":false},{"id":1080784,"name":"Hubert Schorle","orcid":"0000-0001-8272-0076","position":8,"is_corresponding":false},{"id":1080783,"name":"Gina Esther Merges","orcid":"0000-0002-5805-965X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>Actl7b</i>\n                    deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>Actin-related proteins (Arps) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp, and is highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b−/−) were infertile, whereas heterozygous males (Actl7b+/−) were fertile. Severe spermatid defects, such as detached acrosomes, disrupted membranes and flagella malformations start to appear after spermiogenesis step 9 in Actl7b−/− mice, finally resulting in spermatogenic arrest. Abnormal spermatids were degraded and levels of autophagy markers were increased. Co-immunoprecipitation with mass spectrometry experiments identified an interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establish that mutations in ACTL7B are directly related to male infertility, pressing for additional research in humans.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37800308","pmcid":"PMC10652042","openalex_id":"https://openalex.org/W4387392712","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"SCHO 503/27-1","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-INF/6762/2020","title":"MS3: New foundations for micro-services and serverless systems"}],"total_grants":3,"fwci":2.1553,"citation_percentile":0.87484415,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://journals.biologists.com/dev/article-pdf/doi/10.1242/dev.201593/3200044/dev201593.pdf","host_type":"journal"},{"url":"https://journals.biologists.com/dev/article-pdf/doi/10.1242/dev.201593/3200044/dev201593.pdf","host_type":"publisher"},{"url":"https://journals.biologists.com/dev/article-pdf/doi/10.1242/dev.201593/3239999/dev201593.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/dev.201593","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37800308","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10652042","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10652042","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10652042?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1242/dev.201593","host_type":""},{"url":"https://research-portal.uu.nl/en/publications/4e669c0d-9ec4-48bc-9687-eb0bd120266e","host_type":""},{"url":"https://dspace.library.uu.nl/handle/1874/435099","host_type":""}],"fields_of_study":["Reproductive Biology and Fertility","Sperm and Testicular Function","Renal and related cancers","Animals","Humans","Male","Mice","Actins","Cytoplasmic Dyneins","Dyneins","Semen","Spermatids","Spermatogenesis","Spermatozoa","Testis"],"mesh_terms":["Actins","Animals","Dyneins","Humans","Male","Semen","Spermatids","Spermatogenesis","Spermatozoa","Testis","Mice","Cytoplasmic Dyneins"],"keywords":["Biology","Spermatid","Spermiogenesis","Spermatogenesis","Dynein","Cell biology","Male infertility","Axoneme","Null allele","Sperm","Genetics","Allele","Flagellum","Molecular biology","Microtubule","Gene","Infertility","Endocrinology","Mouse","Actin-related Proteins","Actl7b","Lc8 Light Chains","Male","Cytoplasmic Dyneins","Dyneins","Spermatids","Spermatozoa","Actins","Mice","Semen","Testis","Animals","Humans","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pxd"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T14:09:42.786798Z","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":[]}