{"id":"https://openalex.org/W7214038242","doi":"https://doi.org/10.3390/genes17101165","title":"Animal Model Selection and Deep Phenotyping in Mitochondrial Genetic Diseases: Connecting Human Variants, Multisystem Pathology, and Preclinical Evidence","display_name":"Animal Model Selection and Deep Phenotyping in Mitochondrial Genetic Diseases: Connecting Human Variants, Multisystem Pathology, and Preclinical Evidence","publication_year":2026,"publication_date":"2026-09-22","ids":{"openalex":"https://openalex.org/W7214038242","doi":"https://doi.org/10.3390/genes17101165","pmid":"https://pubmed.ncbi.nlm.nih.gov/42938280","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13704539"},"language":"en","primary_location":{"id":"doi:10.3390/genes17101165","doi":"https://doi.org/10.3390/genes17101165","is_oa":true,"landing_page_url":"https://doi.org/10.3390/genes17101165","pdf_url":null,"source":{"id":"https://openalex.org/S194631498","display_name":"Genes","issn_l":"2073-4425","issn":["2073-4425"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Genes","raw_type":"journal-article"},"volume":null,"type":"review","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/genes17101165","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5015207175","display_name":"Nobuya Sasaki","orcid":"https://orcid.org/0000-0002-7971-3024","observed_orcids":["https://orcid.org/0000-0002-7971-3024"]},"institutions":[{"id":"https://openalex.org/I64189623","display_name":"Kitasato University","ror":"https://ror.org/00f2txz25","country_code":"JP","type":"education","lineage":["https://openalex.org/I64189623"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Nobuya Sasaki","raw_affiliation_strings":["Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Aomori, Japan"],"raw_orcid":"https://orcid.org/0000-0002-7971-3024","affiliations":[{"raw_affiliation_string":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Aomori, Japan","institution_ids":["https://openalex.org/I64189623"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5018199873","display_name":"Masaki Watanabe","orcid":"https://orcid.org/0000-0001-5586-0743","observed_orcids":["https://orcid.org/0000-0001-5586-0743"]},"institutions":[{"id":"https://openalex.org/I64189623","display_name":"Kitasato University","ror":"https://ror.org/00f2txz25","country_code":"JP","type":"education","lineage":["https://openalex.org/I64189623"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Masaki Watanabe","raw_affiliation_strings":["Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Aomori, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada 034-8628, Aomori, Japan","institution_ids":["https://openalex.org/I64189623"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5015207175"],"corresponding_institution_ids":["https://openalex.org/I64189623"],"apc_list":{"value":2600,"currency":"CHF","value_usd":3137},"apc_paid":{"value":2600,"currency":"CHF","value_usd":3137},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.4346116,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":"10","first_page":"1165","last_page":"1165"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12281","display_name":"Animal testing and alternatives","score":0.007300000172108412,"subfield":{"id":"https://openalex.org/subfields/3404","display_name":"Small Animals"},"field":{"id":"https://openalex.org/fields/34","display_name":"Veterinary"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11027","display_name":"Metabolism and Genetic Disorders","score":0.0017000000225380063,"subfield":{"id":"https://openalex.org/subfields/1308","display_name":"Clinical Biochemistry"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/animal-model-selection","display_name":"animal model selection","score":0.9660000205039978},{"id":"https://openalex.org/keywords/deep-phenotyping","display_name":"deep phenotyping","score":0.9829999804496765},{"id":"https://openalex.org/keywords/genetically-modified-mice","display_name":"genetically modified mice","score":0.9129999876022339},{"id":"https://openalex.org/keywords/mitochondrial-heteroplasmy","display_name":"mitochondrial heteroplasmy","score":0.7250000238418579},{"id":"https://openalex.org/keywords/humanized-mouse-model","display_name":"humanized mice","score":0.6460000276565552},{"id":"https://openalex.org/keywords/variant-pathogenicity","display_name":"variant pathogenicity","score":0.8429999947547913},{"id":"https://openalex.org/keywords/3rs","display_name":"3Rs","score":0.6340000033378601},{"id":"https://openalex.org/keywords/mitochondrial-dna-editing","display_name":"mitochondrial DNA editing","score":0.7889999747276306},{"id":"https://openalex.org/keywords/induced-pluripotent-stem-cells","display_name":"induced pluripotent stem cells","score":0.8450000286102295},{"id":"https://openalex.org/keywords/organoids","display_name":"organoids","score":0.9950000047683716},{"id":"https://openalex.org/keywords/automated-phenotyping","display_name":"automated phenotyping","score":0.9760000109672546},{"id":"https://openalex.org/keywords/preclinical-evidence","display_name":"preclinical evidence","score":0.32499998807907104}],"concepts":[{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.7077000141143799},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6801000237464905},{"id":"https://openalex.org/C181561989","wikidata":"https://www.wikidata.org/wiki/Q2581905","display_name":"Heteroplasmy","level":4,"score":0.6679999828338623},{"id":"https://openalex.org/C2777614518","wikidata":"https://www.wikidata.org/wiki/Q935710","display_name":"Mitochondrial disease","level":4,"score":0.667900025844574},{"id":"https://openalex.org/C24586158","wikidata":"https://www.wikidata.org/wiki/Q27075","display_name":"Mitochondrial DNA","level":3,"score":0.6668000221252441},{"id":"https://openalex.org/C2778117688","wikidata":"https://www.wikidata.org/wiki/Q264024","display_name":"Animal model","level":2,"score":0.5349000096321106},{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.5346999764442444},{"id":"https://openalex.org/C2988867146","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Human disease","level":3,"score":0.5300999879837036},{"id":"https://openalex.org/C19843653","wikidata":"https://www.wikidata.org/wiki/Q213907","display_name":"Model organism","level":3,"score":0.47350001335144043},{"id":"https://openalex.org/C112313634","wikidata":"https://www.wikidata.org/wiki/Q7886648","display_name":"Complement (music)","level":5,"score":0.46720001101493835},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.44269999861717224},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4198000133037567},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.3765000104904175},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.35100001096725464},{"id":"https://openalex.org/C7386963","wikidata":"https://www.wikidata.org/wiki/Q3954859","display_name":"Negative selection","level":4,"score":0.3504999876022339},{"id":"https://openalex.org/C2992519594","wikidata":"https://www.wikidata.org/wiki/Q870433","display_name":"Genetic model","level":3,"score":0.33629998564720154},{"id":"https://openalex.org/C2908609012","wikidata":"https://www.wikidata.org/wiki/Q16992002","display_name":"Lawsonia intracellularis","level":2,"score":0.32350000739097595},{"id":"https://openalex.org/C2993056352","wikidata":"https://www.wikidata.org/wiki/Q7432","display_name":"Animal species","level":2,"score":0.30489999055862427},{"id":"https://openalex.org/C2988540567","wikidata":"https://www.wikidata.org/wiki/Q12070446","display_name":"Model system","level":2,"score":0.2921999990940094},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.2709999978542328},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.2694999873638153},{"id":"https://openalex.org/C163950672","wikidata":"https://www.wikidata.org/wiki/Q14905375","display_name":"mitochondrial fusion","level":4,"score":0.2529999911785126},{"id":"https://openalex.org/C36503486","wikidata":"https://www.wikidata.org/wiki/Q11235244","display_name":"Domain (mathematical analysis)","level":2,"score":0.2515000104904175},{"id":"https://openalex.org/C93959086","wikidata":"https://www.wikidata.org/wiki/Q6888345","display_name":"Model selection","level":2,"score":0.25099998712539673}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004195","descriptor_name":"Disease Models, Animal","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D004272","descriptor_name":"DNA, Mitochondrial","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008928","descriptor_name":"Mitochondria","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D010641","descriptor_name":"Phenotype","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D028361","descriptor_name":"Mitochondrial Diseases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D028361","descriptor_name":"Mitochondrial Diseases","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.3390/genes17101165","doi":"https://doi.org/10.3390/genes17101165","is_oa":true,"landing_page_url":"https://doi.org/10.3390/genes17101165","pdf_url":null,"source":{"id":"https://openalex.org/S194631498","display_name":"Genes","issn_l":"2073-4425","issn":["2073-4425"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Genes","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13704539","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13704539/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13704539/pdf/genes-17-01165.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Genes (Basel)","raw_type":"Text"},{"id":"pmid:42938280","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42938280","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Genes","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.3390/genes17101165","doi":"https://doi.org/10.3390/genes17101165","is_oa":true,"landing_page_url":"https://doi.org/10.3390/genes17101165","pdf_url":null,"source":{"id":"https://openalex.org/S194631498","display_name":"Genes","issn_l":"2073-4425","issn":["2073-4425"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Genes","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.8371999859809875,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":98,"referenced_works":["https://openalex.org/W191921287","https://openalex.org/W1548912336","https://openalex.org/W1903699046","https://openalex.org/W1985359371","https://openalex.org/W1988565273","https://openalex.org/W1999871368","https://openalex.org/W2007512651","https://openalex.org/W2009792683","https://openalex.org/W2013070340","https://openalex.org/W2015728354","https://openalex.org/W2019292541","https://openalex.org/W2024595059","https://openalex.org/W2036351079","https://openalex.org/W2038098923","https://openalex.org/W2044897807","https://openalex.org/W2051694207","https://openalex.org/W2053763358","https://openalex.org/W2059793002","https://openalex.org/W2079092251","https://openalex.org/W2088995367","https://openalex.org/W2090038499","https://openalex.org/W2091331379","https://openalex.org/W2094832206","https://openalex.org/W2098813681","https://openalex.org/W2100876024","https://openalex.org/W2106998229","https://openalex.org/W2109232765","https://openalex.org/W2109867174","https://openalex.org/W2121647203","https://openalex.org/W2122267356","https://openalex.org/W2124855292","https://openalex.org/W2129181731","https://openalex.org/W2130230447","https://openalex.org/W2136054837","https://openalex.org/W2143505819","https://openalex.org/W2144944663","https://openalex.org/W2157010532","https://openalex.org/W2191690548","https://openalex.org/W2278345709","https://openalex.org/W2334703889","https://openalex.org/W2407690976","https://openalex.org/W2468765363","https://openalex.org/W2474529975","https://openalex.org/W2518810695","https://openalex.org/W2529339498","https://openalex.org/W2557153205","https://openalex.org/W2598216227","https://openalex.org/W2599467169","https://openalex.org/W2612960139","https://openalex.org/W2617533299","https://openalex.org/W2705861159","https://openalex.org/W2762368071","https://openalex.org/W2765945674","https://openalex.org/W2787981664","https://openalex.org/W2794522909","https://openalex.org/W2887114371","https://openalex.org/W2890448051","https://openalex.org/W2891993984","https://openalex.org/W2901477025","https://openalex.org/W2945275601","https://openalex.org/W2950100524","https://openalex.org/W2968997801","https://openalex.org/W2980030724","https://openalex.org/W3030739213","https://openalex.org/W3031124187","https://openalex.org/W3041877641","https://openalex.org/W3091061565","https://openalex.org/W3093542525","https://openalex.org/W3097294022","https://openalex.org/W3115762724","https://openalex.org/W3129566372","https://openalex.org/W3205253535","https://openalex.org/W3209651303","https://openalex.org/W3215232751","https://openalex.org/W3216939983","https://openalex.org/W3217324349","https://openalex.org/W4210476933","https://openalex.org/W4210874460","https://openalex.org/W4224880055","https://openalex.org/W4236357753","https://openalex.org/W4280623644","https://openalex.org/W4295138696","https://openalex.org/W4362733053","https://openalex.org/W4365146827","https://openalex.org/W4365150372","https://openalex.org/W4379232024","https://openalex.org/W4390561348","https://openalex.org/W4390589383","https://openalex.org/W4398318328","https://openalex.org/W4400407505","https://openalex.org/W4402138409","https://openalex.org/W4403300503","https://openalex.org/W4406948167","https://openalex.org/W4408814358","https://openalex.org/W4410973944","https://openalex.org/W4415992166","https://openalex.org/W7135075568","https://openalex.org/W7166772434"],"related_works":["https://openalex.org/W4328137042","https://openalex.org/W2950809850","https://openalex.org/W2004095141","https://openalex.org/W3093542525","https://openalex.org/W2081713717","https://openalex.org/W2049646847","https://openalex.org/W7097718966","https://openalex.org/W2518810695","https://openalex.org/W3091061565","https://openalex.org/W2474529975"],"abstract_inverted_index":{"Mitochondrial":[0],"genetic":[1],"diseases":[2],"arise":[3],"from":[4,140],"variants":[5],"in":[6,92],"mitochondrial":[7,15],"DNA":[8],"(mtDNA)":[9],"or":[10,97,176],"nuclear":[11],"genes":[12],"required":[13],"for":[14,59,212],"function.":[16],"Although":[17],"many":[18],"involve":[19],"several":[20],"organs,":[21],"the":[22,147,151,194,201],"predominant":[23],"clinical":[24],"manifestations":[25],"may":[26],"be":[27],"confined":[28],"to":[29,36,51,154],"particular":[30,99],"organs.":[31],"Experimental":[32],"models":[33,54,94],"are":[34],"used":[35],"investigate":[37],"variant":[38],"pathogenicity,":[39],"organ":[40,172],"vulnerability,":[41],"disease":[42,114,134],"progression,":[43],"therapeutic":[44],"response,":[45],"and":[46,55,74,78,90,122,128,136,150,174,198,200,209],"safety.":[47],"We":[48,63,102,157,189],"discuss":[49,191],"how":[50],"select":[52],"animal":[53,100],"other":[56],"experimental":[57,148],"systems":[58],"specific":[60],"research":[61],"questions.":[62],"focus":[64],"on":[65,146],"genetically":[66],"engineered":[67],"mice":[68],"(constitutive":[69],"knockout,":[70],"knock-in/humanized,":[71],"conditional/tissue-specific,":[72],"inducible,":[73],"heteroplasmic":[75],"mtDNA":[76,204],"models)":[77],"consider":[79],"when":[80],"yeast,":[81],"worms,":[82],"flies,":[83],"zebrafish,":[84],"rats,":[85],"large":[86],"animals,":[87,89],"companion":[88],"human":[91],"vitro":[93],"can":[95],"complement":[96],"replace":[98],"experiments.":[101],"define":[103],"deep":[104],"phenotyping":[105,211],"by":[106],"five":[107],"minimum":[108],"characteristics:":[109],"longitudinal":[110],"assessment":[111],"across":[112],"defined":[113],"stages;":[115,135],"prespecified":[116],"relationships":[117],"among":[118],"molecular,":[119],"mitochondrial,":[120],"organ,":[121],"whole-animal":[123,175],"measurements;":[124],"integration":[125],"of":[126,138,203],"repeated":[127],"terminal":[129],"endpoints;":[130],"alignment":[131],"with":[132],"patient-relevant":[133,177],"separation":[137],"primary":[139],"exploratory":[141],"outcomes.":[142],"Model":[143],"selection":[144],"depends":[145],"objective":[149],"evidence":[152],"needed":[153],"address":[155],"it.":[156],"also":[158,190],"propose":[159],"a":[160],"multidomain":[161],"framework":[162],"that":[163,181],"distinguishes":[164],"target":[165],"engagement,":[166],"molecular":[167],"correction,":[168],"downstream":[169],"pharmacodynamic":[170],"responses,":[171],"function,":[173],"benefit":[178],"without":[179],"assuming":[180],"effective":[182],"treatments":[183],"must":[184],"improve":[185],"every":[186],"domain":[187],"sequentially.":[188],"reporting":[192],"practices,":[193],"3Rs":[195],"(Replacement,":[196],"Reduction,":[197],"Refinement),":[199],"implications":[202],"editing,":[205],"iPSC-derived":[206],"systems,":[207],"organoids,":[208],"automated":[210],"study":[213],"design.":[214]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-09-23T00:00:00"}
