{"doi":"10.1016/j.mbplus.2020.100053","title":"A glycine substitution in the collagenous domain of Col4a3 in mice recapitulates late onset Alport syndrome","abstract":"Alport syndrome (AS) is a severe inherited glomerulopathy caused by mutations in the genes encoding the α-chains of type-IV collagen, the most abundant component of the extracellular glomerular basement membrane (GBM). Currently most AS mouse models are knockout models for one of the collagen-IV genes. In contrast, about half of AS patients have missense mutations, with single aminoacid substitutions of glycine being the most common. The only mouse model for AS with a homozygous knockin missense mutation, Col4a3-p.Gly1332Glu, was partly described before by our group. Here, a detailed in-depth description of the same mouse is presented, along with another compound heterozygous mouse that carries the glycine substitution in trans with a knockout allele. Both mice recapitulate essential features of AS, including shorten lifespan by 30–35%, increased proteinuria, increased serum urea and creatinine, pathognomonic alternate GBM thinning and thickening, and podocyte foot process effacement. Notably, glomeruli and tubuli respond differently to mutant collagen-IV protomers, with reduced expression in tubules but apparently normal in glomeruli. However, equally important is the fact that in the glomeruli the mutant α3-chain as well as the normal α4/α5 chains seem to undergo a cleavage at, or near the point of the mutation, possibly by the metalloproteinase MMP-9, producing a 35 kDa C-terminal fragment. These mouse models represent a good tool for better understanding the spectrum of molecular mechanisms governing collagen-IV nephropathies and could be used for pre-clinical studies aimed at better treatments for AS.","journal":"Matrix Biology Plus","year":2020,"id":83222,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9324,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":429380,"name":"Isavella Savva","orcid":null,"position":1,"is_corresponding":false},{"id":428444,"name":"Myrtani Pieri","orcid":"0000-0002-8883-4434","position":2,"is_corresponding":false},{"id":428445,"name":"Pavlos Ioannou","orcid":"0000-0003-2659-9261","position":3,"is_corresponding":false},{"id":428446,"name":"Petros Petrou","orcid":"0000-0003-3238-3854","position":4,"is_corresponding":false},{"id":259784,"name":"Gregory Papagregoriou","orcid":"0000-0002-2440-9789","position":5,"is_corresponding":false},{"id":428447,"name":"Kyriaki I. Antoniadou","orcid":"0000-0001-7608-937X","position":6,"is_corresponding":false},{"id":429381,"name":"Neoklis Makrides","orcid":null,"position":7,"is_corresponding":false},{"id":428448,"name":"Charalambos Stefanou","orcid":"0000-0002-0615-986X","position":8,"is_corresponding":false},{"id":263574,"name":"Danica Galešić Ljubanović","orcid":"0000-0002-2850-6316","position":9,"is_corresponding":false},{"id":428449,"name":"Γεώργιος Νικολάου","orcid":"0000-0002-0190-2415","position":10,"is_corresponding":false},{"id":428450,"name":"Dorin‐Bogdan Borza","orcid":"0000-0003-4568-279X","position":11,"is_corresponding":false},{"id":428451,"name":"Kostas Stylianou","orcid":"0000-0003-3678-9421","position":12,"is_corresponding":false},{"id":428452,"name":"Oliver Groß","orcid":"0000-0002-8390-8852","position":13,"is_corresponding":false},{"id":259777,"name":"Constantinos Deltas","orcid":"0000-0001-5549-9169","position":14,"is_corresponding":false},{"id":429379,"name":"Christoforos Odiatis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T21:54:09.383533Z","pmid":"33718859","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":[]}