{"doi":"10.1242/dmm.050473","title":"Transgenic Dendra2::tau expression allows <i>in vivo</i> monitoring of tau proteostasis in <i>Caenorhabditis elegans</i>","abstract":"Protein homeostasis is perturbed in aging-related neurodegenerative diseases called tauopathies, which are pathologically characterized by aggregation of the microtubule-associated protein tau (encoded by the human MAPT gene). Transgenic Caenorhabditis elegans serve as a powerful model organism to study tauopathy disease mechanisms, but moderating transgenic expression level has proven problematic. To study neuronal tau proteostasis, we generated a suite of transgenic strains expressing low, medium or high levels of Dendra2::tau fusion proteins by comparing integrated multicopy transgene arrays with single-copy safe-harbor locus strains generated by recombinase-mediated cassette exchange. Multicopy Dendra2::tau strains exhibited expression level-dependent neuronal dysfunction that was modifiable by known genetic suppressors or an enhancer of tauopathy. Single-copy Dendra2::tau strains lacked distinguishable phenotypes on their own but enabled detection of enhancer-driven neuronal dysfunction. We used multicopy Dendra2::tau strains in optical pulse-chase experiments measuring tau turnover in vivo and found that Dendra2::tau turned over faster than the relatively stable Dendra2. Furthermore, Dendra2::tau turnover was dependent on the protein expression level and independent of co-expression with human TDP-43 (officially known as TARDBP), an aggregating protein interacting with pathological tau. We present Dendra2::tau transgenic C. elegans as a novel tool for investigating molecular mechanisms of tau proteostasis.","journal":"Disease Models & Mechanisms","year":2024,"id":439908,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":351411,"name":"Aleen D. Saxton","orcid":"0000-0002-5055-5755","position":1,"is_corresponding":false},{"id":881800,"name":"Heather N. Currey","orcid":"0000-0001-6428-4880","position":2,"is_corresponding":false},{"id":1251183,"name":"Sarah M. Waldherr","orcid":"0000-0002-8873-4185","position":3,"is_corresponding":false},{"id":355965,"name":"Nicole F. Liachko","orcid":"0000-0003-1250-3871","position":4,"is_corresponding":false},{"id":351412,"name":"Brian C. Kraemer","orcid":"0000-0002-2252-7634","position":5,"is_corresponding":false},{"id":1251586,"name":"Marina Han","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:00:52.633010Z","pmid":"38469687","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":[]}