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Model Systems for Understanding FXPOI

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FXTAS, FXPOI, and Other Premutation Disorders

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Abstract

Fragile X-associated primary ovarian insufficiency is a poorly understood cause of infertility and ovarian insufficiency. Studies to date in humans have been limited for the most part to studies of the epidemiology and natural history of the condition in women. However, related Repeat Expansion Diseases as well as cell and animal model systems are beginning to provide vital insights into the mechanisms that might be responsible for disease pathology.

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References

  • Allen EG, Sullivan AK, Marcus M, Small C, Dominguez C, Epstein MP, Charen K, He W, Taylor KC, Sherman SL (2007) Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod 22(8):2142–2152

    Article  CAS  PubMed  Google Scholar 

  • Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stutzer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y (2014) A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response. Cell 157(4):869–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ascano M Jr, Mukherjee N, Bandaru P, Miller JB, Nusbaum JD, Corcoran DL, Langlois C, Munschauer M, Dewell S, Hafner M, Williams Z, Ohler U, Tuschl T (2012) FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature 492(7429):382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atsma F, Bartelink ML, Grobbee DE, Van Der Schouw YT (2006) Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause 13(2):265–279

    Article  PubMed  Google Scholar 

  • Bachner D, Manca A, Steinbach P, Wohrle D, Just W, Vogel W, Hameister H, Poustka A (1993) Enhanced expression of the murine FMR1 gene during germ cell proliferation suggests a special function in both the male and the female gonad. Hum Mol Genet 2(12):2043–2050

    Article  CAS  PubMed  Google Scholar 

  • Banez-Coronel M, Porta S, Kagerbauer B, Mateu-Huertas E, Pantano L, Ferrer I, Guzman M, Estivill X, Marti E (2012) A pathogenic mechanism in Huntington’s disease involves small CAG-repeated RNAs with neurotoxic activity. PLoS Genet 8(2):e1002481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bione S, Benedetti S, Goegan M, Menditto I, Marozzi A, Ferrari M, Toniolo D (2006) Skewed X-chromosome inactivation is not associated with premature ovarian failure in a large cohort of Italian patients. Am J Med Genet A 140(12):1349–1351

    Article  PubMed  Google Scholar 

  • Brouwer JR, Severijnen E, De Jong FH, Hessl D, Hagerman RJ, Oostra BA, Willemsen R (2008) Altered hypothalamus-pituitary-adrenal gland axis regulation in the expanded CGG-repeat mouse model for fragile X-associated tremor/ataxia syndrome. Psychoneuroendocrinology 33(6):863–873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buijsen RA, Sellier C, Severijnen LA, Oulad-Abdelghani M, Verhagen RF, Berman RF, Charlet-Berguerand N, Willemsen R, Hukema RK (2014) FMRpolyG-positive inclusions in CNS and non-CNS organs of a fragile X premutation carrier with fragile X-associated tremor/ataxia syndrome. Acta Neuropathol Commun 2:162

    Article  PubMed  PubMed Central  Google Scholar 

  • Caudy AA, Myers M, Hannon GJ, Hammond SM (2002) Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev 16(19):2491–2496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang MC, Decaro JJ, Zheng M, Gearing M, Shubeck L, Sherman SL, Welt CK (2011) Ovarian histopathological and ubiquitin-immunophenotypic features in fragile X-associated primary ovarian insufficiency: a study of five cases and selected controls. Histopathology 59(5):1018–1023

    Article  PubMed  PubMed Central  Google Scholar 

  • Chonchaiya W, Schneider A, Hagerman RJ (2009) Fragile X: a family of disorders. Adv Pediatr 56:165–186

    Article  PubMed  PubMed Central  Google Scholar 

  • Cleary JD, Ranum LP (2013) Repeat-associated non-ATG (RAN) translation in neurological disease. Hum Mol Genet 22(R1):R45–R51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleary JD, Ranum LP (2014) Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders. Curr Opin Genet Dev 26:6–15

    Article  CAS  PubMed  Google Scholar 

  • Costa A, Wang Y, Dockendorff TC, Erdjument-Bromage H, Tempst P, Schedl P, Jongens TA (2005) The Drosophila fragile X protein functions as a negative regulator in the orb autoregulatory pathway. Dev Cell 8(3):331–342

    Article  CAS  PubMed  Google Scholar 

  • Deeks AA, Gibson-Helm M, Teede H, Vincent A (2011) Premature menopause: a comprehensive understanding of psychosocial aspects. Climacteric 14(5):565–572

    Article  CAS  PubMed  Google Scholar 

  • Ennis S, Ward D, Murray A (2006) Nonlinear association between CGG repeat number and age of menopause in FMR1 premutation carriers. Eur J Hum Genet 14(2):253–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Entezam A, Biacsi R, Orrison B, Saha T, Hoffman GE, Grabczyk E, Nussbaum RL, Usdin K (2007) Regional FMRP deficits and large repeat expansions into the full mutation range in a new Fragile X premutation mouse model. Gene 395(1–2):125–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Epstein AM, Bauer CR, Ho A, Bosco G, Zarnescu DC (2009) Drosophila Fragile X protein controls cellular proliferation by regulating cbl levels in the ovary. Dev Biol 330(1):83–92

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Zhang F, Lokey LK, Chastain JL, Lakkis L, Eberhart D, Warren ST (1995) Translational suppression by trinucleotide repeat expansion at FMR1. Science 268(5211):731–734

    Article  CAS  PubMed  Google Scholar 

  • Ferder I, Parborell F, Sundblad V, Chiauzzi V, Gomez K, Charreau EH, Tesone M, Dain L (2013) Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat. Reproduction 145(4):335–343

    Article  CAS  PubMed  Google Scholar 

  • Gallagher JC (2007) Effect of early menopause on bone mineral density and fractures. Menopause 14(3 Pt 2):567–571

    Article  PubMed  Google Scholar 

  • Galloway JN, Shaw C, Yu P, Parghi D, Poidevin M, Jin P, Nelson DL (2014) CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome. Hum Mol Genet 23(22):5906–5915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Arocena D, Yang JE, Brouwer JR, Tassone F, Iwahashi C, Berry-Kravis EM, Goetz CG, Sumis AM, Zhou L, Nguyen DV, Campos L, Howell E, Ludwig A, Greco C, Willemsen R, Hagerman RJ, Hagerman PJ (2010) Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet 19(2):299–312

    Article  CAS  PubMed  Google Scholar 

  • Greco CM, Hagerman RJ, Tassone F, Chudley AE, Del Bigio MR, Jacquemont S, Leehey M, Hagerman PJ (2002) Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125(Pt 8):1760–1771

    Article  CAS  PubMed  Google Scholar 

  • Hagerman RJ, Leehey M, Heinrichs W, Tassone F, Wilson R, Hills J, Grigsby J, Gage B, Hagerman PJ (2001) Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 57(1):127–130

    Article  CAS  PubMed  Google Scholar 

  • Handa V, Saha T, Usdin K (2003) The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 31(21):6243–6248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Handa V, Goldwater D, Stiles D, Cam M, Poy G, Kumari D, Usdin K (2005) Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles. FEBS Lett 579(12):2702–2708

    Article  CAS  PubMed  Google Scholar 

  • Hashem V, Galloway JN, Mori M, Willemsen R, Oostra BA, Paylor R, Nelson DL (2009) Ectopic expression of CGG containing mRNA is neurotoxic in mammals. Hum Mol Genet 18(13):2443–2451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He F, Krans A, Freibaum BD, Taylor JP, Todd PK (2014) TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet 23(19):5036–5051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffman GE, Le W, Entezam A, Otsuka N, Tong Z-B, Nelson L, Flaws JA, Mcdonald JH, Jafar S, Usdin K (2012) Ovarian abnormalities in a mouse model of Fragile X-associated primary ovarian insufficiency. J Histochem Cytochem 60(6):439–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hukema RK, Buijsen RA, Raske C, Severijnen LA, Nieuwenhuizen-Bakker I, Minneboo M, Maas A, De Crom R, Kros JM, Hagerman PJ, Berman RF, Willemsen R (2014) Induced expression of expanded CGG RNA causes mitochondrial dysfunction in vivo. Cell Cycle 13(16):2600–2608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ, Hukema RK (2011) Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta Neuropathol 122(4):467–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunter JE, Epstein MP, Tinker SW, Charen KH, Sherman SL (2008) Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity. Genet Epidemiol 32(6):553–559

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishizuka A, Siomi MC, Siomi H (2002) A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 16(19):2497–2508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwahashi CK, Yasui DH, An HJ, Greco CM, Tassone F, Nannen K, Babineau B, Lebrilla CB, Hagerman RJ, Hagerman PJ (2006) Protein composition of the intranuclear inclusions of FXTAS. Brain 129(Pt 1):256–271

    CAS  PubMed  Google Scholar 

  • Jin P, Zarnescu DC, Zhang F, Pearson CE, Lucchesi JC, Moses K, Warren ST (2003) RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron 39(5):739–747

    Article  CAS  PubMed  Google Scholar 

  • Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J, Jongens TA, Nelson DL, Moses K, Warren ST (2004) Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 7(2):113–117

    Article  CAS  PubMed  Google Scholar 

  • Jin P, Duan R, Qurashi A, Qin Y, Tian D, Rosser TC, Liu H, Feng Y, Warren ST (2007) Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. Neuron 55(4):556–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalantaridou SN, Naka KK, Papanikolaou E, Kazakos N, Kravariti M, Calis KA, Paraskevaidis EA, Sideris DA, Tsatsoulis A, Chrousos GP, Michalis LK (2004) Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy. J Clin Endocrinol Metab 89(8):3907–3913

    Article  CAS  PubMed  Google Scholar 

  • Kenneson A, Zhang F, Hagedorn CH, Warren ST (2001) Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum Mol Genet 10(14):1449–1454

    Article  CAS  PubMed  Google Scholar 

  • Khalili K, Del Valle L, Muralidharan V, Gault WJ, Darbinian N, Otte J, Meier E, Johnson EM, Daniel DC, Kinoshita Y, Amini S, Gordon J (2003) Puralpha is essential for postnatal brain development and developmentally coupled cellular proliferation as revealed by genetic inactivation in the mouse. Mol Cell Biol 23(19):6857–6875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krol J, Fiszer A, Mykowska A, Sobczak K, De Mezer M, Krzyzosiak WJ (2007) Ribonuclease dicer cleaves triplet repeat hairpins into shorter repeats that silence specific targets. Mol Cell 25(4):575–586

    Article  CAS  PubMed  Google Scholar 

  • Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U (2001) Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum Mol Genet 10(4):329–338

    Article  CAS  PubMed  Google Scholar 

  • Lee JE, Cooper TA (2009) Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans 37(Pt 6):1281–1286

    Article  CAS  PubMed  Google Scholar 

  • Lee KY, Li M, Manchanda M, Batra R, Charizanis K, Mohan A, Warren SA, Chamberlain CM, Finn D, Hong H, Ashraf H, Kasahara H, Ranum LP, Swanson MS (2013) Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol Med 5(12):1887–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei ZM, Mishra S, Zou W, Xu B, Foltz M, Li X, Rao CV (2001) Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. Mol Endocrinol 15(1):184–200

    Article  CAS  PubMed  Google Scholar 

  • Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, Duan EK, Hsueh AJ (2010) Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A 107(22):10280–10284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y, Tang C, He H, Duan R (2013) Activation of mTOR ameliorates fragile X premutation rCGG repeat-mediated neurodegeneration. PLoS One 8(4):e62572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu C, Lin L, Tan H, Wu H, Sherman SL, Gao F, Jin P, Chen D (2012) Fragile X premutation RNA is sufficient to cause primary ovarian insufficiency in mice. Hum Mol Genet 21(23):5039–5047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig AL, Espinal GM, Pretto DI, Jamal AL, Arque G, Tassone F, Berman RF, Hagerman PJ (2014) CNS expression of murine fragile X protein (FMRP) as a function of CGG-repeat size. Hum Mol Genet 23(12):3228–3238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maclaran K, Horner E, Panay N (2010) Premature ovarian failure: long-term sequelae. Menopause Int 16(1):38–41

    PubMed  Google Scholar 

  • Mailick MR, Hong J, Greenberg J, Smith L, Sherman S (2014) Curvilinear association of CGG repeats and age at menopause in women with FMR1 premutation expansions. Am J Med Genet B Neuropsychiatr Genet 165B(8):705–711

    Article  CAS  PubMed  Google Scholar 

  • Mankodi A, Urbinati CR, Yuan QP, Moxley RT, Sansone V, Krym M, Henderson D, Schalling M, Swanson MS, Thornton CA (2001) Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. Hum Mol Genet 10(19):2165–2170

    Article  CAS  PubMed  Google Scholar 

  • Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, Swanson MS (2000) Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J 19(17):4439–4448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray A, Ennis S, Morton N (2000) No evidence for parent of origin influencing premature ovarian failure in fragile X premutation carriers. Am J Hum Genet 67(1):253–254, author reply 256-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Napoli E, Ross-Inta C, Wong S, Omanska-Klusek A, Barrow C, Iwahashi C, Garcia-Arocena D, Sakaguchi D, Berry-Kravis E, Hagerman R, Hagerman PJ, Giulivi C (2011) Altered zinc transport disrupts mitochondrial protein processing/import in fragile X-associated tremor/ataxia syndrome. Hum Mol Genet 20(15):3079–3092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh SY, He F, Krans A, Frazer M, Taylor JP, Paulson HL, Todd PK (2015) RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome. Hum Mol Genet 24(15):4317–4326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palaniappan M, Menon KM (2010) Human chorionic gonadotropin stimulates theca-interstitial cell proliferation and cell cycle regulatory proteins by a cAMP-dependent activation of AKT/mTORC1 signaling pathway. Mol Endocrinol 24(9):1782–1793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peier AM, Nelson DL (2002) Instability of a premutation-sized CGG repeat in FMR1 YAC transgenic mice. Genomics 80(4):423–432

    Article  CAS  PubMed  Google Scholar 

  • Primerano B, Tassone F, Hagerman RJ, Hagerman P, Amaldi F, Bagni C (2002) Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations. RNA 8(12):1482–1488

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qurashi A, Li W, Zhou JY, Peng J, Jin P (2011) Nuclear accumulation of stress response mRNAs contributes to the neurodegeneration caused by Fragile X premutation rCGG repeats. PLoS Genet 7(6):e1002102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ranum LP, Cooper TA (2006) RNA-mediated neuromuscular disorders. Annu Rev Neurosci 29:259–277

    Article  CAS  PubMed  Google Scholar 

  • Reddy P, Adhikari D, Zheng W, Liang S, Hamalainen T, Tohonen V, Ogawa W, Noda T, Volarevic S, Huhtaniemi I, Liu K (2009) PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Hum Mol Genet 18(15):2813–2824

    Article  CAS  PubMed  Google Scholar 

  • Rife M, Nadal A, Mila M, Willemsen R (2004) Immunohistochemical FMRP studies in a full mutated female fetus. Am J Med Genet A 124A(2):129–132

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Revenga L, Madrigal I, Alegret M, Santos M, Mila M (2008) Evidence of depressive symptoms in fragile-X syndrome premutated females. Psychiatr Genet 18(4):153–155

    Article  PubMed  Google Scholar 

  • Rodriguez-Revenga L, Madrigal I, Pagonabarraga J, Xuncla M, Badenas C, Kulisevsky J, Gomez B, Mila M (2009) Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet 17(10):1359–1362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross-Inta C, Omanska-Klusek A, Wong S, Barrow C, Garcia-Arocena D, Iwahashi C, Berry-Kravis E, Hagerman RJ, Hagerman PJ, Giulivi C (2010) Evidence of mitochondrial dysfunction in fragile X-associated tremor/ataxia syndrome. Biochem J 429(3):545–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki J, Nakashima N (2000) Methionine-independent initiation of translation in the capsid protein of an insect RNA virus. Proc Natl Acad Sci U S A 97(4):1512–1515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schluter EW, Hunsaker MR, Greco CM, Willemsen R, Berman RF (2012) Distribution and frequency of intranuclear inclusions in female CGG KI mice modeling the fragile X premutation. Brain Res 1472:124–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sellier C, Rau F, Liu Y, Tassone F, Hukema RK, Gattoni R, Schneider A, Richard S, Willemsen R, Elliott DJ, Hagerman PJ, Charlet-Berguerand N (2010) Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J 29(7):1248–1261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sellier C, Freyermuth F, Tabet R, Tran T, He F, Ruffenach F, Alunni V, Moine H, Thibault C, Page A, Tassone F, Willemsen R, Disney MD, Hagerman PJ, Todd PK, Charlet-Berguerand N (2013) Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome. Cell Rep 3(3):869–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherman SL (2000) Premature ovarian failure in the fragile X syndrome. Am J Med Genet 97(3):189–194

    Article  CAS  PubMed  Google Scholar 

  • Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA (2010) Premature menopause or early menopause: long-term health consequences. Maturitas 65(2):161–166

    Article  PubMed  Google Scholar 

  • Sofola OA, Jin P, Qin Y, Duan R, Liu H, De Haro M, Nelson DL, Botas J (2007) RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron 55(4):565–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spath MA, Nillesen WN, Smits AP, Feuth TB, Braat DD, Van Kessel AG, Yntema HG (2010) X chromosome inactivation does not define the development of premature ovarian failure in fragile X premutation carriers. Am J Med Genet A 152A(2):387–393

    Article  CAS  PubMed  Google Scholar 

  • Spath MA, Feuth TB, Smits AP, Yntema HG, Braat DD, Thomas CM, Van Kessel AG, Sherman SL, Allen EG (2011) Predictors and risk model development for menopausal age in fragile X premutation carriers. Genet Med 13(7):643–650

    Article  PubMed  PubMed Central  Google Scholar 

  • Streuli I, Fraisse T, Ibecheole V, Moix I, Morris MA, De Ziegler D (2009) Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency. Fertil Steril 92(2):464–470

    Article  CAS  PubMed  Google Scholar 

  • Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, Yadav-Shah M, Sherman SL (2005) Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 20(2):402–412

    Article  CAS  PubMed  Google Scholar 

  • Sullivan SD, Welt C, Sherman S (2011) FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med 29(4):299–307

    Article  PubMed  Google Scholar 

  • Takahashi N, Tarumi W, Itoh MT, Ishizuka B (2015) The stage- and cell type-specific localization of fragile X mental retardation protein in rat ovaries. Reprod Sci 22(12):1524–1529

    Article  CAS  PubMed  Google Scholar 

  • Taneja KL, Mccurrach M, Schalling M, Housman D, Singer RH (1995) Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J Cell Biol 128(6):995–1002

    Article  CAS  PubMed  Google Scholar 

  • Tassone F, Hagerman RJ, Chamberlain WD, Hagerman PJ (2000a) Transcription of the FMR1 gene in individuals with fragile X syndrome. Am J Med Genet 97(3):195–203

    Article  CAS  PubMed  Google Scholar 

  • Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ (2000b) Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 66(1):6–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tassone F, Iwahashi C, Hagerman PJ (2004) FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia syndrome (FXTAS). RNA Biol 1(2):103–105

    Article  CAS  PubMed  Google Scholar 

  • Tassone F, Beilina A, Carosi C, Albertosi S, Bagni C, Li L, Glover K, Bentley D, Hagerman PJ (2007) Elevated FMR1 mRNA in premutation carriers is due to increased transcription. RNA 13(4):555–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tejada MI, Garcia-Alegria E, Bilbao A, Martinez-Bouzas C, Beristain E, Poch M, Ramos-Arroyo MA, Lopez B, Fernandez Carvajal I, Ribate MP, Ramos F (2008) Analysis of the molecular parameters that could predict the risk of manifesting premature ovarian failure in female premutation carriers of fragile X syndrome. Menopause 15(5):945–949

    Article  PubMed  Google Scholar 

  • Todd PK, Oh SY, Krans A, Pandey UB, Di Prospero NA, Min KT, Taylor JP, Paulson HL (2010) Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genet 6(12):e1001240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione KM, Basrur V, Elenitoba-Johnson K, Vonsattel JP, Louis ED, Sutton MA, Taylor JP, Mills RE, Charlet-Berguerand N, Paulson HL (2013) CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron 78(3):440–455

    Article  CAS  PubMed  Google Scholar 

  • Vega EM, Egea MA, Mautalen CA (1994) Influence of the menopausal age on the severity of osteoporosis in women with vertebral fractures. Maturitas 19(2):117–124

    Article  CAS  PubMed  Google Scholar 

  • Welt CK, Smith PC, Taylor AE (2004) Evidence of early ovarian aging in fragile X premutation carriers. J Clin Endocrinol Metab 89(9):4569–4574

    Article  CAS  PubMed  Google Scholar 

  • Willemsen R, Hoogeveen-Westerveld M, Reis S, Holstege J, Severijnen LA, Nieuwenhuizen IM, Schrier M, Van Unen L, Tassone F, Hoogeveen AT, Hagerman PJ, Mientjes EJ, Oostra BA (2003) The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum Mol Genet 12(9):949–959

    Article  CAS  PubMed  Google Scholar 

  • Yaba A, Bianchi V, Borini A, Johnson J (2008) A putative mitotic checkpoint dependent on mTOR function controls cell proliferation and survival in ovarian granulosa cells. Reprod Sci 15(2):128–138

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Duan R, Chen D, Wang J, Chen D, Jin P (2007) Fragile X mental retardation protein modulates the fate of germline stem cells in Drosophila. Hum Mol Genet 16(15):1814–1820

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Xu S, Xia L, Wang J, Wen S, Jin P, Chen D (2009) The bantam microRNA is associated with drosophila fragile X mental retardation protein and regulates the fate of germline stem cells. PLoS Genet 5(4):e1000444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zumwalt M, Ludwig A, Hagerman PJ, Dieckmann T (2007) Secondary structure and dynamics of the r(CGG) repeat in the mRNA of the fragile X mental retardation 1 (FMR1) gene. RNA Biol 4(2):93–100

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by an award (NS091859) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS) to SLS and funding from the Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases to KU (DK057808 08).

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Authors and Affiliations

  1. Section on Gene Structure and Disease, LCMB, NIDDK, NIH, Bethesda, MD, USA

    Karen Usdin

  2. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

    Renate K. Hukema

  3. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA

    Stephanie L. Sherman

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  1. Karen Usdin
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  2. Renate K. Hukema
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  3. Stephanie L. Sherman
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Correspondence to Karen Usdin .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California, Davis, California, USA

    Flora Tassone

  2. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA

    Deborah A. Hall

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Usdin, K., Hukema, R.K., Sherman, S.L. (2016). Model Systems for Understanding FXPOI. In: Tassone, F., Hall, D. (eds) FXTAS, FXPOI, and Other Premutation Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-33898-9_11

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