Expression of FMRpolyG in peripheral blood mononuclear cells of women with fragile X mental retardation 1 gene premutation

• Verfasst von: Nguyen, Xuan Phuoc [VerfasserIn]
• Verfasst von: Vilkaite, Adriana [VerfasserIn]
• Verfasst von: Messmer, Birgitta [VerfasserIn]
• Verfasst von: Dietrich, Jens Erik [VerfasserIn]
• Verfasst von: Hinderhofer, Katrin [VerfasserIn]
• Verfasst von: Schäkel, Knut [VerfasserIn]
• Verfasst von: Strowitzki, Thomas [VerfasserIn]
• Verfasst von: Rehnitz, Julia [VerfasserIn]
• Titel: Expression of FMRpolyG in peripheral blood mononuclear cells of women with fragile X mental retardation 1 gene premutation
• Verf.angabe: Xuan Phuoc Nguyen, Adriana Vilkaite, Birgitta Messmer, Jens E. Dietrich, Katrin Hinderhofer, Knut Schäkel, Thomas Strowitzki and Julia Rehnitz
• E-Jahr: 2022
• Jahr: 1 March 2022
• Umfang: 13 S.
• Fussnoten: Gesehen am 05.04.2022
• Titel Quelle: Enthalten in: Genes
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2022
• Band/Heft Quelle: 13(2022), 3, Artikel-ID 451, Seite 1-3
• ISSN Quelle: 2073-4425
• DOI: doi:10.3390/genes13030451
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: <i>FMR1</i> premutation
• Sach-SW: FMRpolyG
• Sach-SW: premature ovarian insufficiency
• K10plus-PPN: 1797618458
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Fragile X-associated primary ovarian insufficiency (FXPOI) is characterized by oligo/amenorrhea and hypergonadotropic hypogonadism and is caused by the expansion of the CGG repeat in the 5′UTR of Fragile X Mental Retardation 1 (FMR1). Approximately 20% of women carrying an FMR1 premutation (PM) allele (55-200 CGG repeat) develop FXPOI. Repeat Associated Non-AUG (RAN)-translation dependent on the variable CGG-repeat length is thought to cause FXPOI, due to the production of a polyglycine-containing FMR1 protein, FMRpolyG. Peripheral blood monocyte cells (PBMCs) and granulosa cells (GCs) were collected to detect FMRpolyG and its cell type-specific expression in FMR1 PM carriers by immunofluorescence staining (IF), Western blotting (WB), and flow cytometric analysis (FACS). For the first time, FMRpolyG aggregates were detected as ubiquitin-positive inclusions in PBMCs from PM carriers, whereas only a weak signal without inclusions was detected in the controls. The expression pattern of FMRpolyG in GCs was comparable to that in the lymphocytes. We detected FMRpolyG as a 15- to 25-kDa protein in the PBMCs from two FMR1 PM carriers, with 124 and 81 CGG repeats. Flow cytometric analysis revealed that FMRpolyG was significantly higher in the T cells from PM carriers than in those from non-PM carriers. The detection of FMRpolyG aggregates in the peripheral blood and granulosa cells of PM carriers suggests that it may have a toxic potential and an immunological role in ovarian damage in the development of FXPOI.