Knockout of RNA binding protein MSI2 impairs follicle development in the mouse ovary: characterization of MSI1 and MSI2 during folliculogenesis
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- dc.contributor.author Sutherland, Jessie M.ca
- dc.contributor.author Sobinoff, Alexander P.ca
- dc.contributor.author Gunter, Kara M.ca
- dc.contributor.author Fraser, Barbara A.ca
- dc.contributor.author Pye, Victoriaca
- dc.contributor.author Bernstein, Ilana R.ca
- dc.contributor.author Boon, Evanca
- dc.contributor.author Siddall, Nicole A.ca
- dc.contributor.author Andrés, Luisa Deca
- dc.contributor.author Hime, Gary R.ca
- dc.contributor.author Holt, Janet E.ca
- dc.contributor.author Graf, T. (Thomas)ca
- dc.contributor.author McLaughlin, Eileen A.ca
- dc.date.accessioned 2015-11-11T19:32:36Z
- dc.date.available 2015-11-11T19:32:36Z
- dc.date.issued 2015
- dc.description.abstract Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.en
- dc.format.mimetype application/pdfca
- dc.identifier.citation Sutherland JM Sobinoff AP, Gunter KM, Fraser BA, Pye V, Bernstein IR et al. Knockout of RNA binding protein MSI2 impairs follicle development in the mouse ovary: characterization of MSI1 and MSI2 during folliculogenesis. Biomolecules. 2015;5(3):1228-44. DOI: 10.3390/biom5031228en
- dc.identifier.doi http://dx.doi.org/10.3390/biom5031228
- dc.identifier.issn 2218-273X
- dc.identifier.uri http://hdl.handle.net/10230/25057
- dc.language.iso engca
- dc.publisher MDPIca
- dc.relation.ispartof Biomolecules. 2015;5(3):1228-44
- dc.rights © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).en
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
- dc.subject.keyword Fertilityen
- dc.subject.keyword Musashien
- dc.subject.keyword Oocyteen
- dc.subject.keyword Granulosa cellen
- dc.subject.keyword Oogenesisen
- dc.subject.other Fecunditatca
- dc.subject.other Ratolins (Animals de laboratori) -- Embriologiaca
- dc.title Knockout of RNA binding protein MSI2 impairs follicle development in the mouse ovary: characterization of MSI1 and MSI2 during folliculogenesisen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca