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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.
dc.contributor.author Sobinoff, Alexander P.
dc.contributor.author Gunter, Kara M.
dc.contributor.author Fraser, Barbara A.
dc.contributor.author Pye, Victoria
dc.contributor.author Bernstein, Ilana R.
dc.contributor.author Boon, Evan
dc.contributor.author Siddall, Nicole A.
dc.contributor.author Andrés, Luisa De
dc.contributor.author Hime, Gary R.
dc.contributor.author Holt, Janet E.
dc.contributor.author Graf, T. (Thomas)
dc.contributor.author McLaughlin, Eileen A.
dc.date.accessioned 2015-11-11T19:32:36Z
dc.date.available 2015-11-11T19:32:36Z
dc.date.issued 2015
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): 1228-1244. DOI 10.3390/biom5031228
dc.identifier.issn 2218-273X
dc.identifier.uri http://hdl.handle.net/10230/25057
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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Biomolecules. 2015; 5(3): 1228-1244
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/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Fecunditat
dc.subject.other Ratolins (Animals de laboratori) -- Embriologia
dc.title Knockout of RNA binding protein MSI2 impairs follicle development in the mouse ovary: characterization of MSI1 and MSI2 during folliculogenesis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/biom5031228
dc.subject.keyword Fertility
dc.subject.keyword Musashi
dc.subject.keyword Oocyte
dc.subject.keyword Granulosa cell
dc.subject.keyword Oogenesis
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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