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Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis

School of Environmental and Life Sciences, University of Newcastle, Callaghan NSW 2308, Australia
School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan NSW 2308, Australia
Anatomy and Neuroscience, University of Melbourne, Parkville VIC 3010, Australia
Differentiation and Cancer Program, Center for Genomic Regulation and UPF, Barcelona 08000, Spain
Author to whom correspondence should be addressed.
Academic Editor: André P. Gerber
Biomolecules 2015, 5(3), 1228-1244;
Received: 11 March 2015 / Revised: 29 May 2015 / Accepted: 9 June 2015 / Published: 26 June 2015
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
PDF [3815 KB, uploaded 26 June 2015]


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. View Full-Text
Keywords: fertility; Musashi; oocyte; granulosa cell; oogenesis fertility; Musashi; oocyte; granulosa cell; oogenesis

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Sutherland, J.M.; Sobinoff, A.P.; Gunter, K.M.; Fraser, B.A.; Pye, V.; Bernstein, I.R.; Boon, E.; Siddall, N.A.; De Andres, L.I.; Hime, G.R.; Holt, J.E.; Graf, T.; McLaughlin, E.A. Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis. Biomolecules 2015, 5, 1228-1244.

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