Heterozygous Eif4nif1 Stop-Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.

• Tác giả: Kenneth Ivan Aston, Robert A Campbell, Benjamin Emery, Emma R James, Lihua Liu, Mika Moriwaki, Ashley M O'Connor, Neal D Tolley, Corrine K Welt
• Ngôn ngữ: eng
• Ký hiệu phân loại: 364.134 Offenses against administration of justice
• Thông tin xuất bản: United States : Endocrinology , 2025
• Bộ sưu tập: NCBI
• ID: 60813

Tóm tắt

 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.