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Heterozygous Eif4nif1 Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.
Heterozygous Eif4nif1 Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.
- Source :
-
Endocrinology [Endocrinology] 2025 Feb 05; Vol. 166 (3). - Publication Year :
- 2025
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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.<br /> (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 166
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 39827467
- Full Text :
- https://doi.org/10.1210/endocr/bqaf014