Cargando…

Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation

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) alle...

Descripción completa

Detalles Bibliográficos
Autores principales: Nguyen, Xuan Phuoc, Vilkaite, Adriana, Messmer, Birgitta, Dietrich, Jens E., Hinderhofer, Katrin, Schäkel, Knut, Strowitzki, Thomas, Rehnitz, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951797/
https://www.ncbi.nlm.nih.gov/pubmed/35328005
http://dx.doi.org/10.3390/genes13030451
_version_ 1784675472183918592
author Nguyen, Xuan Phuoc
Vilkaite, Adriana
Messmer, Birgitta
Dietrich, Jens E.
Hinderhofer, Katrin
Schäkel, Knut
Strowitzki, Thomas
Rehnitz, Julia
author_facet Nguyen, Xuan Phuoc
Vilkaite, Adriana
Messmer, Birgitta
Dietrich, Jens E.
Hinderhofer, Katrin
Schäkel, Knut
Strowitzki, Thomas
Rehnitz, Julia
author_sort Nguyen, Xuan Phuoc
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8951797
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89517972022-03-26 Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation Nguyen, Xuan Phuoc Vilkaite, Adriana Messmer, Birgitta Dietrich, Jens E. Hinderhofer, Katrin Schäkel, Knut Strowitzki, Thomas Rehnitz, Julia Genes (Basel) Article 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. MDPI 2022-03-01 /pmc/articles/PMC8951797/ /pubmed/35328005 http://dx.doi.org/10.3390/genes13030451 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nguyen, Xuan Phuoc
Vilkaite, Adriana
Messmer, Birgitta
Dietrich, Jens E.
Hinderhofer, Katrin
Schäkel, Knut
Strowitzki, Thomas
Rehnitz, Julia
Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title_full Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title_fullStr Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title_full_unstemmed Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title_short Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation
title_sort expression of fmrpolyg in peripheral blood mononuclear cells of women with fragile x mental retardation 1 gene premutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951797/
https://www.ncbi.nlm.nih.gov/pubmed/35328005
http://dx.doi.org/10.3390/genes13030451
work_keys_str_mv AT nguyenxuanphuoc expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT vilkaiteadriana expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT messmerbirgitta expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT dietrichjense expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT hinderhoferkatrin expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT schakelknut expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT strowitzkithomas expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation
AT rehnitzjulia expressionoffmrpolyginperipheralbloodmononuclearcellsofwomenwithfragilexmentalretardation1genepremutation