title: Primary Ovarian Insufficiency Induced by Fanconi Anemia E Mutation in a Mouse Model.
abstract: In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model.
authors.affiliation: Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Chun
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Khurshida
authors.initials: K
authors.lastname: Begum
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Overbeek
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000235:genetics; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D052239:Fanconi Anemia Complementation Group E Protein / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016254:Mutagenesis, Insertional; D009154:Mutation; D006080:Ovarian Follicle / Q000378:metabolism* / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D019076:Transgenes
chemical_list: D052239:Fanconi Anemia Complementation Group E Protein