LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Publisher: Elsevier
Languages: English
Types: Article
Subjects:

Numerous experimental models have been developed to reiterate endophenotypes of Rett syndrome, a neurodevelopmental disorder with a multitude of motor, cognitive and vegetative symptoms. Here, female Mecp2Stop mice [1] were characterised at mild symptomatic conditions in tests for anxiety (open field, elevated plus maze) and home cage observation systems for food intake, locomotor activity and circadian rhythms.

\ud \ud

Aged 8–9 months, Mecp2Stop mice presented with heightened body weight, lower overall activity in the open field, but no anxiety phenotype. Although home cage activity scans conducted in two different observation systems, PhenoMaster and PhenoTyper, confirmed normal circadian activity, they revealed severely compromised habituation to a novel environment in all parameters registered including those derived from a non-linear decay model such as initial exploration maximum, decay half-life of activity and span, as well as plateau. Furthermore, overall activity was significantly reduced in nocturnal periods due to reductions in both fast ambulatory movements, but also a slow lingering. In contrast, light-period activity profiles during which the amount of sleep was highest remained normal in Mecp2Stop mice.

\ud \ud

These data confirm the slow and progressive development of Rett-like symptoms in female Mecp2Stop mice resulting in a prominent reduction of overall locomotor activity, while circadian rhythms are maintained. Alterations in the time-course of habituation may indicate deficiencies in cognitive processing.

  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • [1] Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science 2007;315:1143-7.
    • [2] Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome. Report of 35 cases. Annals of Neurology 1983;14:471-9.
    • [3] Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X linked MECP2, encoding methyl-Cp G binding protein 2. Nature Genetics 1999;23:185-8.
    • [4] Chen RZ, Akbarian S, Tudor M, Jaenisch R. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nature Genetics 2001;27:327-31.
    • [5] Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nature Genetics 2001;27:322-6.
    • [6] Shahbazian M, Young JI, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, et al. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 2002;35:243-54.
    • [7] Watson CM, Pelka GJ, Radziewic T, Shahbazian MD, Christodoulou J, Williamson SL, et al. Reduced proportion of Purkinje cells expressing paternally derived mutant Mecp2308 allele in female mouse cerebellum is not due to a skewed primary pattern of X-chromosome inactivation. Human Molecular Genetics 2005;14(13):1851-61.
    • [8] Young JI, Zoghbi HY. X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mouse model of Rett syndrome. American Journal of Human Genetics 2004;74:511-20.
    • [9] Reiss AL, Faruque F, Naidu S, AbramsM. Beaty T, Bryan RN, et al. Neuroanatomy of Rett syndrome: a volumetric imaging study. Annals of Neurology 1993;34:227-34.
    • [10] Gotoh H, Suzuki I, Maruki K, Miomo M, Hirasawa K, Sasaki N. Magnetic resonance imaging and clinical findings examined in adulthood-studies on three adults with Rett syndrome. Brain and Development 2001;23(Suppl. 1):S121-88.
    • [11] Murakami JW, Courchesne E, Haas RH, Press GA, Yeung-Courchesne R. Cerebellar, cerebral abnormalities in Rett syndrome: a quantitative MR analysis. American Journal of Roentgenology 1992;159:177-83.
    • [12] Saywell V, Viola A, Confort-Gouny S, Le Fur Y, Villard L, Cozzone PJ. Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism. Biochemical and Biophysical Research Communications 2006;340:776-83.
    • [13] Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM. Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biological Psychiatry 2006;59:468-76.
    • [14] Pratte M, Panayotis N, Ghata A, Villard L, Roux JC. Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice. Behavioural Brain Research 2011;216:313-20.
    • [15] Santos M, Silva-Fernandes A, Oliveira P, Sousa N, Maciel P. Evidence for abnormal early development in a mouse model of Rett syndrome. Genes, Brain and Behavior 2007;6:277-86.
    • [16] Samaco RC, McGraw CM, Ward CS, Sun Y, Neul JL, Zoghbi HY. Female Mecp2+/− mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies. Human Molecular Genetics 2013;22:96-109.
    • [17] Adachi M, Autry AE, Covington HE, Monteggia LM. MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. Journal of Neuroscience 2009;29(13):4218-27.
    • [18] De Filippis B, Ricceri L, Laviola G. Early postnatal behavioral changes in the Mecp 2-308 truncation mouse model of Rett syndrome. Genes, Brain and Behavior 2010;9:213-23.
    • [19] Fyffe SL, Neul JL, Samaco RC, Chao HT, Ben-Shachar S, Moretti P, et al. Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress. Neuron 2008;59:947-58.
    • [20] Lonetti G, Angelucci A, Morando L, Boggio EM, Giustetto M, Pizzorusso T. Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biological Psychiatry 2010;67:657-65.
    • [21] McGill BE, Bundle SF, Yaylaoglu MB, Carson JP, Thaller C, Zoghbi HY. Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome. Proceedings of the National Academy of Sciences of the United States of America 2006;103:18267-72.
    • [22] Stearns NA, Schaevitz LR, Bowling H, Nag N, Berger UV, Berger-Sweeney J. Behavioral, anatomical abnormalities in Mecp2 mutant mice: a model for Rett syndrome. Neuroscience 2007;146:907-21.
    • [23] De Filippis B, Ricceri L, Fuso A, Laviola G. Neonatal exposure to low dose corticosterone persistently modulates hippocampal mineralocorticoid receptor expression and improves locomotor/exploratory behaviour in a mouse model of Rett syndrome. Neuropharmacology 2013;68:174-83.
    • [24] Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. British Journal of Pharmacology 2009;156:1154-66.
    • [25] Glaze DG, Frost Jr JD, Zoghbi HY, Percy AK. Rett's syndrome: characterization of respiratory patterns and sleep. Annals of Neurology 1987;21:377-82.
    • [26] Nomura Y. Early behavior characteristics and sleep disturbance in Rett syndrome. Brain and Development 2005;27:S35-42.
    • [27] Zappella M, Meloni I, Longo I, Hayek G, Renieri A. Preserved speech variants of the Rett syndrome: molecular and clinical analysis. American Journal of Medical Genetics 2001;104:14-22.
    • [28] Kerr B, Alvarez-Saavedra M, Saez MA, Saona A, Young JI. Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypomorphic mice. Human Molecular Genetics 2008;17:1707-17.
    • [29] LaSalle JM. Paradoxical role of methyl-CpG-binding protein 2 in Rett syndrome. Current Topics in Developmental Biology 2004;59:61-86.
    • [30] Ricceri L, De Filippis B, Laviola G. Mouse models of Rett syndrome: from behavioural phenotyping to preclinical evaluation of new therapeutic approaches. Behavioural Pharmacology 2008;19:501-17.
    • [31] Robinson L, Guy J, McKay L, Brockett E, Spike RC, Selfridge J, et al. Morphological and functional reversal of phenotypes in a mouse model of Rett syndrome. Brain 2012;April [Epub ahead of print].
    • [32] Edelsbrunner ME, Painsipp E, Herzog H, Holzer P. Evidence from knockout mice for distinct implications of neuropeptide-Y Y2 and Y4 receptors in the circadian control of locomotion: exploration, water and food intake. Neuropeptides 2009;43(6):491-7.
    • [33] Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, et al. Ghrelin action in the brain controls adipocyte metabolism. Journal of Clinical Investigation 2006;116(7):1983-93.
    • [34] Motulsky H, Christopoulos A. Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fitting. San Diego: GraphPad Software Inc; 2003.
    • [35] Caeyenberghs K, Balschun D, Roces DP, Schwake M, Saftig P, D'Hooge R. Multivariate neurocognitive and emotional profile of a mannosidosis murine model for therapy assessment. Neurobiology of Disease 2006;23(2):422-32.
    • [36] de Visser L, van den Bos R, Spruijt BM. Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion. Behavioural Brain Research 2005;160(2):382-8.
    • [37] Young D, Nagarajan L, de Klerk N, Jacoby P, Ellaway C, Leonard H. Sleep problems in Rett syndrome. Brain and Development 2007;29(10):609-16.
    • [38] Alvarez-Saavedra M, Antoun G, Yanagiya A, Oliva-Hernandez R, Cornejo-Palma D, Perez-Iratxeta C, et al. miRNA-132 orchestrates chromatin remodelling and translational control of the circadian clock. Human Molecular Genetics 2011;20(4):731-51.
    • [39] De Filippis B, Fabbri A, Simone D, Canese R, Ricceri L, Malchiodi-Albedi F, et al. Modulation of RhoGTPases improves the behavioural phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome. Neuropsychopharmacology 2012;37:1152-63.
    • [40] Giacometti E, Luikenhuis S, Beard C, Jaenisch R. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proceedings of the National Academy of Sciences of the United States of America 2007;104:1931-6.
    • [41] Samaco RC, Fryer JD, Ren J, Fyffe S, Chao HT, Sun Y, et al. A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. Human Molecular Genetics 2008;17:1718-27.
    • [42] Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320:1224-9.
    • [43] Pelka GJ, Watson CM, Radziewic T, Hayward M, Lahooti H, Christodoulou J, et al. Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice. Brain 2006;129:887-98.
    • [44] Bissonette JM, Knopps SJ. Separate respiratory phenotypes in methyl-CpGbinding protein 2 (Mecp2) deficient mice. Pediatric Research 2006;59:513-8.
    • [45] Bissonette JM, Knopps SJ. Effect of inspired oxygen on periodic breathing in methyl-CpG-binding protein 2 (Mecp2) deficient mice. Journal of Applied Physiology 2008;104:198-204.
    • [46] Bissonette JM, Knopps SJ, Maylie J, Thong T. Autonomic cardiovascular control in methyl-CpG-binding protein 2 (Mecp2) deficient mice. Autonomic Neuroscience 2007;136:82-9.
    • [47] Blardi P, De Lalla A, D'Ambrogio T, Zappella M, Cevenini G, Ceccatelli L, et al. Rett syndrome and plasma leptin levels. Journal of Pediatrics 2007;150(1):37-9.
    • [48] Pilcová R, Sulcová J, Hill M, Bláha P, Lisá L. Leptin levels in obese children: effects of gender, weight reduction and androgens. Physiological Research 2003;52(1):53-60.
    • [49] Alvarez-Saavedra M, Saez MA, Kang D, Zoghbi HY, Young JI. Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. Human Molecular Genetics 2007;16(19):2315-25.
    • [50] Jugloff DG, Vandamme K, Logan R, Visanji NP, Brotchie JM, Eubanks JH. Targeted delivery of a Mecp2 transgene to forebrain neuronsimproves the behavior of female Mecp2-deficient mice. Human Molecular Genetics 2008;17:1386-96.
    • [51] Abdala APL, Dutschmann M, Bissonette JM, Paton JFR. Correction of respiratory disorders in a mouse model of Rett syndrome. Proceedings of the National Academy of Sciences of the United States of America 2010;107:18208-13.
    • [52] Moretti P, Bouwknecht JA, Teague R, Paylor R, Zoghbi HY. Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Human Molecular Genetics 2005;14:205-20.
    • [53] Kondo M, Gray LJ, Pelka GJ, Christodoulou J, Tam PP, Hannan AJ. Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome-Mecp2 gene dosage effects and BDNF expression. European Journal of Neuroscience 2008;27:3342-50.
    • [54] Chao HT, Zoghbi HY. MeCP2: only 100% will do. Nature Neuroscience 2012;15:176-7.
    • [55] Mount RH, Charman T, Hastings RP, Reilly S, Cass H. The Rett syndrome behaviour questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. Journal of Child Psychology and Psychiatry and Allied Disciplines 2002;43:1099-110.
    • [56] Hagberg B. Clinical manifestations and stages of Rett Syndrome. Mental Retardation and Developmental Disabilities Research Reviews 2002;8:61-5.
    • [57] Kazlaukas V, Schuh J, Dall'Igna OP, Pereira GS, Bonan CD, Lara DR. Behavioral and cognitive profile of mice with high and low exploratory phenotypes. Behavioural Brain Research 2005;162:272-8.
    • [58] Plomin R. Genetics and general cognitive ability. Nature 1999;402(Suppl.):C25-9.
    • [59] Langthorne P, McGill P, O'Reilly M. Incorporating “motivation” into the functional analysis of challenging behavior: on the interactive and integrative potential of the motivating operation. Behavior Modification 2007;31(4):466-87.
    • [60] Niedermeyer E. Frontal lobe disinhibition: Rett syndrome and attention deficit hyperactivity disorder. Clinical Electroencephalography 2001;32(1):20-3.
    • [61] Niedermeyer E, Naidu SB. Rett syndrome, EEG and the motor cortex as a model for better understanding of attention deficit hyperactivity disorder (ADHD). European Child and Adolescent Psychiatry 1998;7(2):69-72 [review].
    • [62] Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 2006;1(4):1-11.
    • [63] Piazza CC, Fisher W, Kiesewetter K, Bowman L, Moser H. Aberrant sleep patterns in children with Rett syndrome. Brain and Development 1990;12: 488-93.
  • No related research data.
  • No similar publications.

Share - Bookmark

Download from

Cite this article