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Introduction: Reminiscing on Models and Modeling

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Modeling Fragile X Syndrome

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 54))

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Abstract

This chapter answers three basic questions, which are: (1) Why build models, (2) why build models of fragile X syndrome, and (3) what has been learned from the models of fragile X syndrome that have been made? The first question is used to frame the other two questions, providing the appropriate context by which the rest of the book should be examined. Of necessity the last two questions are only addressed briefly, and from one man’s point of view, as they contain the subject matter of the entirety of the book. Thus, the reader is introduced to the various topics under review and urged to read for him/herself their contents, drawing such conclusions as he/she thinks are warranted.

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References

  • Bat O, Kimmel M, Axelrod DE (1997) Computer simulation of expansions of DNA triplet repeats in the fragile X syndrome and Huntington’s disease. J Theor Biol 188:53–67

    Article  PubMed  CAS  Google Scholar 

  • Bennetto L, Pennington BF (1996) The neuropsychology of fragile X syndrome. In: Hagerman RJ, Cronister A (eds) Fragile X syndrome: diagnosis, treatment and research. The Johns Hopkins University Press, Baltimore, pp 210–248

    Google Scholar 

  • Bloom H (2002) Genius: a mosaic of one hundred exemplary creative minds. Warner Books, New York

    Google Scholar 

  • Brown V, Jin P, Ceman S, Darnell JC, O’Donnell WT, Tenenbaum SA, Jin X, Feng Y, Wilkinson KD, Keene JD (2001) Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107:477–487

    Article  PubMed  CAS  Google Scholar 

  • Burne T, Scott E, van Swinderen B, Hilliard M, Reinhard J, Claudianos C, Eyles D, McGrath J (2011) Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish? Mol Psychiatry 16:7–16

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Yun S-W, Seto J, Liu W, Toth M (2003) The fragile x mental retardation protein binds and regulates a novel class of mRNAs containing U-rich target sequences. Neuroscience 120:1005–1017

    Article  PubMed  CAS  Google Scholar 

  • Clapp K, Tranfaglia M (2011) Diagnosis and Treatment. www.fraxa.org

  • Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, Greenough WT (1997) Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci USA 94:5401–5404

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Holmes A (2005) The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 4:775–790

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, MartĂ­nez Cerdeño V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF, Noctor SC (2011) Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Hum Mol Genet 20:64–79

    Article  PubMed  CAS  Google Scholar 

  • Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB (2001) Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107:489–499

    Article  PubMed  CAS  Google Scholar 

  • Darnell JC, Fraser CE, Mostovetsky O, Stefani G, Jones TA, Eddy SR, Darnell RB (2005) Kissing complex RNAs mediate interaction between the fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev 19:903–918

    Article  PubMed  CAS  Google Scholar 

  • Denman RB (2008) FXR1P: the fragile X family member involved in muscle development. In: Denman RB (ed) RNA binding proteins in development and disease. India: Research Signpost, Trivandrum, pp 123–138

    Google Scholar 

  • Dolzhanskaya N, Merz G, Aletta JM, Denman RB (2006) Methylation regulates FMRP’s intracellular protein–protein and protein–RNA interactions. J Cell Sci 119:1933–1946

    Article  PubMed  CAS  Google Scholar 

  • Elvira G, Wasiak S, Blandford V, Tong X-K, Serrano A, Fan X, del Rayo Sanchez-Carbente M, Servant F, Bell AW, Boismenu D, Lacaille J-C, McPherson PS, DesGroseillers L, Sossin WS (2006) Characterization of an RNA granule from developing brain. Mol Cell Proteomics 5:635–651

    PubMed  CAS  Google Scholar 

  • Evanko D (2007) Windows on the brain. Nat Meth 4:474

    Article  CAS  Google Scholar 

  • Fiandaca MS, Bankiewicz KS (2010) Gene therapy for Parkinson’s disease: from non-human primates to humans. Curr Opin Mol Ther 12:519–529

    PubMed  CAS  Google Scholar 

  • Gessert S, Bugner V, Tecza A, Pinker M, KĂĽhl M (2010) FMR1/FXR1 and the miRNA pathway are required for eye and neural crest development. Dev Biol 341:222–235

    Article  PubMed  CAS  Google Scholar 

  • Hagerman PJ, Hagerman RJ (2004) Fragile X-associated tremor/ataxia syndrome (FXTAS). Ment Retard Dev Disabil Res Rev 10:25–30

    Article  PubMed  Google Scholar 

  • Hinton V, Brown WT, Wisniewski K, Rudelli R (1991) Analysis of the neocortex of three male with the fragile X syndrome. Am J Med Gen 41(3):289–294

    Article  CAS  Google Scholar 

  • Houle D, Govindaraju DR, Omholt S (2010) Phenomics: the next challenge. Nat Rev Genet 11:855–866

    Article  PubMed  CAS  Google Scholar 

  • Huot M-E, Bisson N, Davidovic L, Mazroui R, Labelle Y, Moss T, Khandjian EW (2005) The RNA-binding protein fragile X-related 1 regulates somite formation in Xenopus laevis. Mol Biol Cell 16(9):4350–4361

    Article  PubMed  CAS  Google Scholar 

  • Kanai Y, Dohmae N, Hirokawa N (2004) Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43:513–525

    Article  PubMed  CAS  Google Scholar 

  • Kao D-I, Aldridge GM, Weiler IJ, Greenough WT (2010) Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci USA 107:15601–15606

    Article  PubMed  CAS  Google Scholar 

  • Kay BK, Peng HB (eds) (1991) Xenopus laevis: practical uses in cell and molecular biology. Harcourt Brace Jovanovich, New York

    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 10:1449–1454

    Article  PubMed  CAS  Google Scholar 

  • Koukoui SD, Chaudhuri A (2007) Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome. Brain Res Rev 53:27–37

    Article  PubMed  CAS  Google Scholar 

  • Krichevsky AM, Kosik KS (2001) Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation. Neuron 32:683–696

    Article  PubMed  CAS  Google Scholar 

  • Luo X, Nerlick S, An W, King ML (2011) Xenopus germline nanos1 is translationally repressed by a novel structure-based mechanism. Development 138:589–598

    Article  PubMed  CAS  Google Scholar 

  • Miyashiro KY, Beckel-Mitchener A, Purk TP, Becker KG, Barret T, Liu L, Carbonetto S, Weiler IJ, Greenough WT, Eberwine J (2003) RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37:417–431

    Article  PubMed  CAS  Google Scholar 

  • Oostra BA, Willemsen R (2003) A fragile balance: FMR1 expression levels. Hum Mol Genet 12:R249–R257

    Article  PubMed  CAS  Google Scholar 

  • Pacey LKK, Doering LC (2007) Developmental expression of FMRP in the astrocyte lineage: implications for fragile X syndrome. Glia 55:1601–1609

    Article  PubMed  Google Scholar 

  • Peal D, Peterson R, Milan D (2010) Small molecule screening in Zebrafish. J Cardiovasc Transl Res 3:454–460

    Article  PubMed  Google Scholar 

  • Pienaar IS, Götz J, Feany MB (2010) Parkinson’s disease: Insights from non-traditional model organisms. Prog Neurobiol 92:558–571

    Article  PubMed  CAS  Google Scholar 

  • Rao A, Steward O (1991) Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. J Neurosci 11:2881–2895

    PubMed  CAS  Google Scholar 

  • Raymond FL (2006) X-linked mental retardation: a clinical guide. J Med Genet 43(3):193–200

    Article  PubMed  CAS  Google Scholar 

  • Russell B (1912) Problems of philosophy. Bookjungle, Champaign

    Google Scholar 

  • Schaeffer C, Bardoni B, Mandel J-L, Ehresmann B, Ehresmann C, Moine H (2001) The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J 20:4803–4813

    Article  PubMed  CAS  Google Scholar 

  • Sigler A, Murphy TH (2010) In vivo 2-photon imaging of fine structure in the rodent brain: before, during, and after stroke. Stroke 41:S117–S123

    Article  PubMed  Google Scholar 

  • Steenbergen PJ, Richardson MK, Champagne DL (2011) The use of the zebrafish model in stress research. Prog Neuropsychopharmacol Biol Psychiatry (In Press, Corrected Proof)

    Google Scholar 

  • Sung Y-J, Hwang M-CC, Hwang Y-W (1996) The dominant negative effects of H-Ras harboring a Gly to Ala mutation at position 60. J Biol Chem 271:30537–30543

    Article  PubMed  CAS  Google Scholar 

  • Sung Y-J, Conti J, Currie JR, Brown WT, Denman RB (2000) RNAs that interact with the fragile X syndrome RNA binding protein FMRP. Biochem Biophys Res Commun 275:973–980

    Article  PubMed  CAS  Google Scholar 

  • van Tijn P, Kamphuis W, Marlatt MW, Hol EM, Lucassen PJ (2011) Presenilin mouse and zebrafish models for dementia: focus on neurogenesis. Prog Neurobiol 93(2):149–164

    Article  PubMed  Google Scholar 

  • Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914

    Article  PubMed  CAS  Google Scholar 

  • Vogel G (2010) Diseases in a dish take off. Science 330:1172–1173

    Article  PubMed  CAS  Google Scholar 

  • Waung MW, Huber KM (2009) Protein translation in synaptic plasticity: mGluR-LTD, Fragile X. Curr Opin Neurobiol 19:319–326

    Article  PubMed  CAS  Google Scholar 

  • Xie W, Denman RB (2011) Protein methylation and stress granules: Post-translational modifier or innocent bystander? Mol Biol Int pp 1–14, Article ID: 137459

    Google Scholar 

  • Zeier Z, Kumar A, Bodhinathan K, Feller JA, Foster TC, Bloom DC (2009) Fragile X mental retardation protein replacement restores hippocampal synaptic function in a mouse model of fragile X syndrome. Gene Ther 16:1122–1129

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Frias MA, Mele A, Ruggiu M, Eom T, Marney CB, Wang H, Licatalosi DD, Fak JJ, Darnell RB (2010) Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329:439–443

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Robert B. Denman .

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Denman, R.B. (2012). Introduction: Reminiscing on Models and Modeling. In: Denman, R. (eds) Modeling Fragile X Syndrome. Results and Problems in Cell Differentiation, vol 54. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21649-7_1

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