title: Ovarian abnormalities in a mouse model of fragile X primary ovarian insufficiency.
abstract: FMR1 premutation (PM) alleles have 55-200 CGG·CCG-repeats in their 5' UTR. PM carriers are at risk of fragile X-associated tremor and ataxia syndrome (FXTAS). Females are also at risk for FX primary ovarian insufficiency (FXPOI). PM pathology is generally attributed to deleterious properties of transcripts with long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle pool. Whether this is due to a smaller than normal original follicle pool or an increased rate of follicle depletion is unclear. A FX-PM mouse the authors generated with 130 CGG·CCG-repeats in the endogenous Fmr1 gene recapitulates features of FXTAS. Here the authors demonstrate that the gross development of the ovary and the establishment of the primordial follicle pool is normal in these mice. However, these animals show a faster loss of follicles of all follicle classes, suggesting that the problem is intrinsic to the ovary. In addition, many oocytes show aberrant nuclear accumulation of FMRP and elevated levels of ubiquitination. Furthermore, PM follicles are smaller and have fewer granulosa cells (GCs) than normal. Thus, these animals have ovarian abnormalities involving both the oocytes and GCs that may shed light on the molecular basis of FXPOI in humans.
authors.affiliation: Department of Biology, Morgan State University, Baltimore, MD 21251, USA. gl042@verizon.net
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Hoffman
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Le
authors.forename: Ali
authors.initials: A
authors.lastname: Entezam
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Tong
authors.forename: Lawrence
authors.initials: L
authors.lastname: Nelson
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
authors.forename: John H
authors.initials: JH
authors.lastname: McDonald
authors.forename: Sanjeeda
authors.initials: S
authors.lastname: Jafar
authors.forename: Karen
authors.initials: K
authors.lastname: Usdin
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005496:Follicular Atresia; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D006107:Granulosa Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000378:metabolism / Q000473:pathology*; D054875:Ubiquitination
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse