Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary

Characterization of msi1 and msi2 during folliculogenesis

Jessie M. Sutherland, Alexander P. Sobinoff, Kara M. Gunter, Barbara A. Fraser, Victoria Pye, Ilana R. Bernstein, Evan Boon, Nicole A. Siddall, Luisa I. De Andres, Gary R. Hime, Janet E. Holt, Thomas Graf, Eileen A. McLaughlin

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1228-1244
Number of pages17
JournalBiomolecules
Volume5
Issue number3
DOIs
Publication statusPublished - 7 Jul 2015
Externally publishedYes

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RNA-Binding Proteins
Oocytes
Fertility
Ovary
Litter Size
Mammals
Spermatogenesis
Xenopus
Knockout Mice
Drosophila
Animals
Proteins
Genes
Messenger RNA
Chemical analysis
Research
Antral

Cite this

Sutherland, Jessie M. ; Sobinoff, Alexander P. ; Gunter, Kara M. ; Fraser, Barbara A. ; Pye, Victoria ; Bernstein, Ilana R. ; Boon, Evan ; Siddall, Nicole A. ; De Andres, Luisa I. ; Hime, Gary R. ; Holt, Janet E. ; Graf, Thomas ; McLaughlin, Eileen A. / Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary : Characterization of msi1 and msi2 during folliculogenesis. In: Biomolecules. 2015 ; Vol. 5, No. 3. pp. 1228-1244.
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title = "Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary: Characterization of msi1 and msi2 during folliculogenesis",
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.",
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author = "Sutherland, {Jessie M.} and Sobinoff, {Alexander P.} and Gunter, {Kara M.} and Fraser, {Barbara A.} and Victoria Pye and Bernstein, {Ilana R.} and Evan Boon and Siddall, {Nicole A.} and {De Andres}, {Luisa I.} and Hime, {Gary R.} and Holt, {Janet E.} and Thomas Graf and McLaughlin, {Eileen A.}",
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Sutherland, JM, Sobinoff, AP, Gunter, KM, Fraser, BA, Pye, V, Bernstein, IR, Boon, E, Siddall, NA, De Andres, LI, Hime, GR, Holt, JE, Graf, T & McLaughlin, EA 2015, 'Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary: Characterization of msi1 and msi2 during folliculogenesis', Biomolecules, vol. 5, no. 3, pp. 1228-1244. https://doi.org/10.3390/biom5031228

Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary : Characterization of msi1 and msi2 during folliculogenesis. / Sutherland, Jessie M.; Sobinoff, Alexander P.; Gunter, Kara M.; Fraser, Barbara A.; Pye, Victoria; Bernstein, Ilana R.; Boon, Evan; Siddall, Nicole A.; De Andres, Luisa I.; Hime, Gary R.; Holt, Janet E.; Graf, Thomas; McLaughlin, Eileen A.

In: Biomolecules, Vol. 5, No. 3, 07.07.2015, p. 1228-1244.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary

T2 - Characterization of msi1 and msi2 during folliculogenesis

AU - Sutherland, Jessie M.

AU - Sobinoff, Alexander P.

AU - Gunter, Kara M.

AU - Fraser, Barbara A.

AU - Pye, Victoria

AU - Bernstein, Ilana R.

AU - Boon, Evan

AU - Siddall, Nicole A.

AU - De Andres, Luisa I.

AU - Hime, Gary R.

AU - Holt, Janet E.

AU - Graf, Thomas

AU - McLaughlin, Eileen A.

PY - 2015/7/7

Y1 - 2015/7/7

N2 - 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.

AB - 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.

KW - Fertility

KW - Granulosa cell

KW - Musashi

KW - Oocyte

KW - Oogenesis

KW - RNA-Binding Proteins/genetics

KW - Gene Knockout Techniques

KW - Ovarian Follicle/growth & development

KW - Animals

KW - Gene Expression Regulation, Developmental

KW - Female

KW - Mice

KW - Nerve Tissue Proteins/deficiency

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UR - http://www.mendeley.com/research/knockout-rna-binding-protein-msi2-impairs-follicle-development-mouse-ovary-characterization-msi1-msi-1

U2 - 10.3390/biom5031228

DO - 10.3390/biom5031228

M3 - Article

VL - 5

SP - 1228

EP - 1244

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 3

ER -