{"doi":"10.1210/endocr/bqaf014","title":"Heterozygous <i>Eif4nif1</i> Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women","abstract":"We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The Eif4enif1 C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.1286C>G stop-gain mutation in exon 10. The hybrid offspring of CMV-Cre mice with Eif4enif1WT/flx mice were designated Eif4enif1WT/Δ for simplicity. A subset of female heterozygotes (Eif4enif1WT/Δ) had no litters. In those with litters, the final litter was earlier (5.4 ± 2.6 vs 10.5 ± 0.7 months; P = .02). Heterozygous breeding pair (Eif4enif1WT/Δ × Eif4enif1WT/Δ) litter size was 60% of WT litter size (3.9 ± 2.0 vs 6.5 ± 3.0 pups/litter; P < .001). The genotypes were 35% Eif4enif1WT/flx and 65% Eif4enif1WT/Δ, with no homozygotes. Homozygote embryos did not develop beyond the 4- to 8-cell stage. The number of follicles in ovaries from Eif4enif1WT/Δ mice was lower starting at the primordial (499 ± 290 vs 1445 ± 381) and primary follicle stage (1069 ± 346 vs 1450 ± 193) on day 10 (P < .05). The preantral follicle number was lower starting on day 21 (213 ± 86 vs 522 ± 227; P < .01). Examination of ribosome protected mRNAs demonstrated altered mRNA expression. The Eif4enif1 stop-gain mice replicate the POI phenotype in women based on an earlier end to reproduction due to oocyte loss. The unique mouse model provides a platform to study regulation of protein translation across oocyte and embryo development in mammals.","journal":"Endocrinology","year":2025,"id":551233,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9374,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1447063,"name":"Lihua Liu","orcid":"0000-0002-5829-9880","position":1,"is_corresponding":false},{"id":854599,"name":"Emma James","orcid":"0000-0001-5680-2131","position":2,"is_corresponding":false},{"id":107320,"name":"Neal D. Tolley","orcid":null,"position":3,"is_corresponding":false},{"id":1447393,"name":"Ashley M O’Connor","orcid":null,"position":4,"is_corresponding":false},{"id":673680,"name":"Benjamin R. Emery","orcid":"0000-0001-5086-6089","position":5,"is_corresponding":false},{"id":1447394,"name":"Kenneth Ivan Aston","orcid":null,"position":6,"is_corresponding":false},{"id":105727,"name":"Robert A. Campbell","orcid":"0000-0003-0027-694X","position":7,"is_corresponding":false},{"id":343992,"name":"Corrine K. Welt","orcid":"0000-0002-8219-5504","position":8,"is_corresponding":false},{"id":567187,"name":"Mika Moriwaki","orcid":"0000-0003-2169-266X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:54:25.065895Z","pmid":"39827467","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":[]}