Dokument: Generierung und Charakterisierung muriner und kamelider Antikörper gegen Reelin
| Titel: | Generierung und Charakterisierung muriner und kamelider Antikörper gegen Reelin | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56038 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210421-112051-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Köber, Sabrina [Autor] | |||||||
| Dateien: |
| |||||||
| Beitragende: | Prof. Dr. Korth, Carsten [Gutachter] Prof. Dr. med. Lang, Philipp [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Zusammenfassung
Reelin ist ein extrazelluläres Matrixprotein das sowohl im embryonalen Gehirn als auch im adulten eine wichtige Rolle spielt. Während der embryonalen Phase sorgt Reelin für eine reguläre Strukturierung des Kortex. Im adulten Gehirn wirkt Reelin positiv auf die Bildung von dendritischen Spines, sowie auf die synaptische Plastizität, ein Hinweis auf einen möglichen Zusammenhang mit Lernen und Gedächtnis. Zur weiteren Untersuchung von Reelin wurden zunächst einzelne Fragmente kloniert und anschließend zur Immunisierung von Mäusen und Lamas genutzt. Im Anschluss erfolgte die Charakterisierung der murinen und kameliden Antikörper sowie die Testung an humanen Proben und in primärer Zellkultur. Im Rahmen der Charakterisierung konnten zwei N-terminale murine Antikörper identifiziert werden, die sowohl Reelin haltiges Zelllysat als auch Reelin haltigen Überstand erkannten (11G11.C6, 20E12.E5). Andere erkannten Reelin nur im gewonnenen Überstand (12G2). Kamelide Antikörper konnten sowohl gegen das N- terminale (24H10) als auch gegen das C- terminale (1949E11) Reelin Fragment identifiziert werden. Bei der Testung der Funktionalität in primären Neuronen konnte im Dab -1 Phosphorylierung Assay kein signifikanter Unterschied nach Zugabe der Antikörper identifiziert werden. Im Stripe Assay jedoch zeigten sich signifikant mehr Neuriten im Reelinstreifen nach Zugeben von 11G11.C6 (p = 0,000009) und 20E12.E5 (p = 0,000008). Die kameliden Antikörper 1949E11 (p = 0,061) und 24H10 (p = 0,092) zeigten ebenfalls tendenziell mehr Neuriten, jedoch ohne Signifikanz. Die Untersuchung von humanen Liquor Proben von Patienten mit Depression, Schizophrenie, Demenz sowie entzündlicher ZNS Erkrankung zeigte im Vergleich zu einer Kontroll- Gruppe keinen signifikanten Unterschied. Jedoch konnte ein signifikant höherer Reelingehalt im Lymphozytenlysat von Patienten mit Schizophrenie im Vergleich zu einer gesunden Kontrollgruppe nachgewiesen werden (p = 0,019). Zusammenfassend konnten wir sowohl kamelide als auch murine N-terminale Antikörper herstellen. C-terminale Antikörper konnten nur als kamelide Antikörper hergestellt werden. Hinweise auf eine Funktionalität der Antikörper konnten gefunden werden, jedoch bei kleiner Testzahl sowie zum Teil widersprüchlichen Ergebnissen der einzelnen Tests untereinander nicht letztlich bewiesen werden. Die murinen Antikörper erkannten zuverlässig Reelin in humanen Proben, wobei Patienten mit Schizophrenie einen höheren Reelingehalt im Lymphozytenlysat, bei insgesamt hoher Variabilität, zeigten.Abstract Reelin is an extracellular matrix protein that is important during brain development as well as in mature brain. While development Reelin forms the regular cortex structure. In the mature brain it is important for generation of dendritic spines as well as synaptic plasticity, so a potential correlation with learning and memory is supposed. For further investigation of Reelin first Reelin fragments were reproduced. These were used for immunization in mouse and lama. After that the mouse and camelid antibodies were characterized and used for testing in human samples and in primary neurons. Two N-terminal mouse antibodies were identified, which bind reelin in positive cell lysates as well as in supernatant (11G11.C6, 20E12.E5). Others only bind Reelin supernatant (12G2). Camelid antibodies could be identified for C-terminus (1949E11) as well as for N-terminus (24H10). Testing in vitro activity in primary neurons, a Dab-1 phosphorylation assay was performed. It showed no significant difference after applying the antibodies. The second test, a stripe assay, showed significant more dendrites in the green stripes after adding (p = 0,000009) and 20E12.E5 (p = 0,000008). After adding camelid antibodies for 1949E11 (p = 0,061) and 24H10 (p = 0,092) a higher amount of dendrites was identified too, but not significant. Investigation of human cerebrospinal fluid samples from patients with depression, schizophrenia, dementia as well as inflammatory disease showed no significant difference in the amount of Reelin. But in human lymphocyte lysate the amount of reelin was significant higher in patients with schizophrenia than in a healthy control group. In summary we could identify camelid and mouse antibodies against N-terminal Reelin. C- terminal antibodies were only identified as camelids. Indication for an in vitro activity could be found, but because of a small test number as well as different results between both tests it could not be proofed. Human Reelin was reliably identified by the mouse antibodies. Patients with schizophrenia had a significant higher amount of Reelin, but a high inter testing variability. | |||||||
| Quelle: | Abraham, H. and G. Meyer (2003). "Reelin-expressing neurons in the postnatal and adult human hippocampal formation." Hippocampus 13(6): 715-727.
Ackermann, R. (1988). "Monoclonal antibodies." Hum Cell 1(1): 46-53. Alcantara, S., M. Ruiz, G. D'Arcangelo, F. Ezan, L. de Lecea, T. Curran, C. Sotelo and E. Soriano (1998). "Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse." J Neurosci 18(19): 7779-7799. Arbabi Ghahroudi, M., A. Desmyter, L. Wyns, R. Hamers and S. Muyldermans (1997). "Selection and identification of single domain antibody fragments from camel heavy-chain antibodies." FEBS Lett 414(3): 521-526. Association, A. P. (2014). Diagnostisches und Statistisches Manual Psychischer Störungen - DSM-5, Hogrefe Verlag. Baneyx, F. (1999). "Recombinant protein expression in Escherichia coli." Curr Opin Biotechnol 10(5): 411-421. Baneyx, F. and M. Mujacic (2004). "Recombinant protein folding and misfolding in Escherichia coli." Nat Biotechnol 22(11): 1399-1408. Beffert, U., E. J. Weeber, A. Durudas, S. Qiu, I. Masiulis, J. D. Sweatt, W. P. Li, G. Adelmann, M. Frotscher, R. E. Hammer and J. Herz (2005). "Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2." Neuron 47(4): 567-579. Berry, M. J. and J. Davies (1992). "Use of antibody fragments in immunoaffinity chromatography. Comparison of FV fragments, VH fragments and paralog peptides." J Chromatogr 597(1-2): 239-245. Bliss, T. V. and T. Lomo (1973). "Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path." J Physiol 232(2): 331-356. Botella-Lopez, A., E. de Madaria, R. Jover, R. Bataller, P. Sancho-Bru, A. Candela, A. Compan, M. Perez-Mateo, S. Martinez and J. Saez-Valero (2008). "Reelin is overexpressed in the liver and plasma of bile duct ligated rats and its levels and glycosylation are altered in plasma of humans with cirrhosis." Int J Biochem Cell Biol 40(4): 766-775. Bradshaw, N. J., S. V. Trossbach, S. Kober, S. Walter, I. Prikulis, S. Weggen and C. Korth (2017). "Disrupted in Schizophrenia 1 regulates the processing of reelin in the perinatal cortex." Schizophr Res. Braff, D., C. Stone, E. Callaway, M. Geyer, I. Glick and L. Bali (1978). "Prestimulus effects on human startle reflex in normals and schizophrenics." Psychophysiology 15(4): 339-343. Brich, J., F. S. Shie, B. W. Howell, R. Li, K. Tus, E. K. Wakeland, L. W. Jin, M. Mumby, G. Churchill, J. Herz and J. A. Cooper (2003). "Genetic modulation of tau phosphorylation in the mouse." J Neurosci 23(1): 187-192. Caviness, V. S., Jr. and P. Rakic (1978). "Mechanisms of cortical development: a view from mutations in mice." Annu Rev Neurosci 1: 297-326. Caviness, V. S., Jr. and R. L. Sidman (1973). "Retrohippocampal, hippocampal and related structures of the forebrain in the reeler mutant mouse." J Comp Neurol 147(2): 235-254. Caviness, V. S., Jr., D. K. So and R. L. Sidman (1972). "The hybrid reeler mouse." J Hered 63(5): 241-246. Chai, X., E. Forster, S. Zhao, H. H. Bock and M. Frotscher (2009). "Reelin stabilizes the actin cytoskeleton of neuronal processes by inducing n-cofilin phosphorylation at serine3." J Neurosci 29(1): 288-299. Chameau, P., D. Inta, T. Vitalis, H. Monyer, W. J. Wadman and J. A. van Hooft (2009). "The N-terminal region of reelin regulates postnatal dendritic maturation of cortical pyramidal neurons." Proc Natl Acad Sci U S A 106(17): 7227-7232. Chang, B. S., F. Duzcan, S. Kim, M. Cinbis, A. Aggarwal, K. A. Apse, O. Ozdel, M. Atmaca, S. Zencir, H. Bagci and C. A. Walsh (2007). "The role of RELN in lissencephaly and neuropsychiatric disease." Am J Med Genet B Neuropsychiatr Genet 144b(1): 58-63. Chen, N., Y. Bao, Y. Xue, Y. Sun, D. Hu, S. Meng, L. Lu and J. Shi (2017). "Meta-analyses of RELN variants in neuropsychiatric disorders." Behav Brain Res 332: 110-119. Chen, Y., U. Beffert, M. Ertunc, T. S. Tang, E. T. Kavalali, I. Bezprozvanny and J. Herz (2005). "Reelin modulates NMDA receptor activity in cortical neurons." J Neurosci 25(36): 8209-8216. Chothia, C., J. Novotny, R. Bruccoleri and M. Karplus (1985). "Domain association in immunoglobulin molecules. The packing of variable domains." J Mol Biol 186(3): 651-663. D'Arcangelo, G., G. G. Miao, S. C. Chen, H. D. Soares, J. I. Morgan and T. Curran (1995). "A protein related to extracellular matrix proteins deleted in the mouse mutant reeler." Nature 374(6524): 719-723. D'Arcangelo, G., K. Nakajima, T. Miyata, M. Ogawa, K. Mikoshiba and T. Curran (1997). "Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody." J Neurosci 17(1): 23-31. Davies, J. and L. Riechmann (1995). "Antibody VH domains as small recognition units." Biotechnology (N Y) 13(5): 475-479. Dazzo, E., M. Fanciulli, E. Serioli, G. Minervini, P. Pulitano, S. Binelli, C. Di Bonaventura, C. Luisi, E. Pasini, S. Striano, P. Striano, G. Coppola, A. Chiavegato, S. Radovic, A. Spadotto, S. Uzzau, A. La Neve, A. T. Giallonardo, O. Mecarelli, S. C. Tosatto, R. Ottman, R. Michelucci and C. Nobile (2015). "Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy." Am J Hum Genet 96(6): 992-1000. de Bergeyck, V., B. Naerhuyzen, A. M. Goffinet and C. Lambert de Rouvroit (1998). "A panel of monoclonal antibodies against reelin, the extracellular matrix protein defective in reeler mutant mice." J Neurosci Methods 82(1): 17-24. de Bergeyck, V., K. Nakajima, C. Lambert de Rouvroit, B. Naerhuyzen, A. M. Goffinet, T. Miyata, M. Ogawa and K. Mikoshiba (1997). "A truncated Reelin protein is produced but not secreted in the 'Orleans' reeler mutation (Reln[rl-Orl])." Brain Res Mol Brain Res 50(1-2): 85-90. Decanniere, K., S. Muyldermans and L. Wyns (2000). "Canonical antigen-binding loop structures in immunoglobulins: more structures, more canonical classes?" J Mol Biol 300(1): 83-91. DeSilva, U., G. D'Arcangelo, V. V. Braden, J. Chen, G. G. Miao, T. Curran and E. D. Green (1997). "The human reelin gene: isolation, sequencing, and mapping on chromosome 7." Genome Res 7(2): 157-164. Desmyter, A., T. R. Transue, M. A. Ghahroudi, M. H. Thi, F. Poortmans, R. Hamers, S. Muyldermans and L. Wyns (1996). "Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme." Nat Struct Biol 3(9): 803-811. DGN, D. (2015, 2015). "Leitlinie Demenz." Retrieved 27.09.2017, from https://www.dgn.org/images/red_leitlinien/LL_2015/PDFs_Download/Demenz/REV_S3-leiltlinie-demenzen.pdf. DGPPN. (2006). "Leitlinie Schizophrenie Kurzversion." Retrieved 27.09.2017, 2017, from https://www.dgppn.de/_Resources/Persistent/a6e04aa47e146de9e159fd2ca1e6987853a055d7/S3_Schizo_Kurzversion.pdf. Doehner, J. and I. Knuesel (2010). "Reelin-mediated Signaling during Normal and Pathological Forms of Aging." Aging Dis 1(1): 12-29. Doehner, J., A. Madhusudan, U. Konietzko, J. M. Fritschy and I. Knuesel (2010). "Co-localization of Reelin and proteolytic AbetaPP fragments in hippocampal plaques in aged wild-type mice." J Alzheimers Dis 19(4): 1339-1357. Dong, E., M. Nelson, D. R. Grayson, E. Costa and A. Guidotti (2008). "Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation." Proc Natl Acad Sci U S A 105(36): 13614-13619. Dumanis, S. B., H. J. Cha, J. M. Song, J. H. Trotter, M. Spitzer, J. Y. Lee, E. J. Weeber, R. S. Turner, D. T. Pak, G. W. Rebeck and H. S. Hoe (2011). "ApoE receptor 2 regulates synapse and dendritic spine formation." PLoS One 6(2): e17203. Durakoglugil, M. S., Y. Chen, C. L. White, E. T. Kavalali and J. Herz (2009). "Reelin signaling antagonizes beta-amyloid at the synapse." Proc Natl Acad Sci U S A 106(37): 15938-15943. Duveau, V., A. Madhusudan, M. Caleo, I. Knuesel and J. M. Fritschy (2011). "Impaired reelin processing and secretion by Cajal-Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy." Hippocampus 21(9): 935-944. Ewert, S., C. Cambillau, K. Conrath and A. Pluckthun (2002). "Biophysical properties of camelid V(HH) domains compared to those of human V(H)3 domains." Biochemistry 41(11): 3628-3636. Falconer, D. S. (1951). "Two new mutants, 'trembler' and 'reeler', with neurological actions in the house mouse (Mus musculus L.)." J Genet 50(2): 192-201. Fatemi, S. H., J. A. Earle and T. McMenomy (2000). "Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression." Mol Psychiatry 5(6): 654-663, 571. Fatemi, S. H., A. V. Snow, J. M. Stary, M. Araghi-Niknam, T. J. Reutiman, S. Lee, A. I. Brooks and D. A. Pearce (2005). "Reelin signaling is impaired in autism." Biol Psychiatry 57(7): 777-787. Fatemi, S. H., J. M. Stary, A. R. Halt and G. R. Realmuto (2001). "Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum." J Autism Dev Disord 31(6): 529-535. Fisher, R. S., C. Acevedo, A. Arzimanoglou, A. Bogacz, J. H. Cross, C. E. Elger, J. Engel, Jr., L. Forsgren, J. A. French, M. Glynn, D. C. Hesdorffer, B. I. Lee, G. W. Mathern, S. L. Moshe, E. Perucca, I. E. Scheffer, T. Tomson, M. Watanabe and S. Wiebe (2014). "ILAE official report: a practical clinical definition of epilepsy." Epilepsia 55(4): 475-482. Forster, E., Y. Jossin, S. Zhao, X. Chai, M. Frotscher and A. M. Goffinet (2006). "Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus." Eur J Neurosci 23(4): 901-909. Franklin, E. C. (1970). "Heavy-chain diseases." N Engl J Med 282(19): 1098-1099. Frotscher, M. (1998). "Cajal-Retzius cells, Reelin, and the formation of layers." Curr Opin Neurobiol 8(5): 570-575. Frotscher, M., C. A. Haas and E. Forster (2003). "Reelin controls granule cell migration in the dentate gyrus by acting on the radial glial scaffold." Cereb Cortex 13(6): 634-640. Galanis, M., R. A. Irving and P. J. Hudson (2001). Bacteriophage Library Construction and Selection of Recombinant Antibodies. Current Protocols in Immunology, John Wiley & Sons, Inc. Gaubner, B. (2017). ICD-10-GM 2017 Systematisches Verzeichnis Deutscher Ärzteverlag. Giovanoli, S., L. Weber and U. Meyer (2014). "Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation." Brain Behav Immun 40: 48-54. Glenner, G. G. and C. W. Wong (1984). "Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein." Biochem Biophys Res Commun 120(3): 885-890. Golde, T. E., S. Estus, L. H. Younkin, D. J. Selkoe and S. G. Younkin (1992). "Processing of the amyloid protein precursor to potentially amyloidogenic derivatives." Science 255(5045): 728-730. Goldman, E. R., G. P. Anderson, J. L. Liu, J. B. Delehanty, L. J. Sherwood, L. E. Osborn, L. B. Cummins and A. Hayhurst (2006). "Facile generation of heat-stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library." Anal Chem 78(24): 8245-8255. Gouras, G. K., J. Tsai, J. Naslund, B. Vincent, M. Edgar, F. Checler, J. P. Greenfield, V. Haroutunian, J. D. Buxbaum, H. Xu, P. Greengard and N. R. Relkin (2000). "Intraneuronal Abeta42 accumulation in human brain." Am J Pathol 156(1): 15-20. Graham, F. K. (1975). "Presidential Address, 1974. The more or less startling effects of weak prestimulation." Psychophysiology 12(3): 238-248. Grehl, H., Reinhardt, F. (2008). Checkliste Neurologie. Stuttgart, Georg Thieme Verlag. Grundke-Iqbal, I., K. Iqbal, Y. C. Tung, M. Quinlan, H. M. Wisniewski and L. I. Binder (1986). "Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology." Proc Natl Acad Sci U S A 83(13): 4913-4917. Grzimek, B. (2000). Grzimeks Tierleben Enzyklopädie des Tierreichs Band 13 Säugetiere. Augsburg, Bechtermünz. Guedj, E., F. Bonini, M. Gavaret, A. Trebuchon, S. Aubert, M. Boucekine, L. Boyer, R. Carron, A. McGonigal and F. Bartolomei (2015). "18FDG-PET in different subtypes of temporal lobe epilepsy: SEEG validation and predictive value." Epilepsia 56(3): 414-421. Guidotti, A., J. Auta, J. M. Davis, V. Di-Giorgi-Gerevini, Y. Dwivedi, D. R. Grayson, F. Impagnatiello, G. Pandey, C. Pesold, R. Sharma, D. Uzunov and E. Costa (2000). "Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study." Arch Gen Psychiatry 57(11): 1061-1069. H., Z. (1987). Monoclonal Antibodies: A Manual of Techniques, CRC Press. Haas, C. A., O. Dudeck, M. Kirsch, C. Huszka, G. Kann, S. Pollak, J. Zentner and M. Frotscher (2002). "Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy." J Neurosci 22(14): 5797-5802. Haas, C. A. and M. Frotscher (2010). "Reelin deficiency causes granule cell dispersion in epilepsy." Exp Brain Res 200(2): 141-149. Haass, C., E. H. Koo, A. Mellon, A. Y. Hung and D. J. Selkoe (1992). "Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments." Nature 357(6378): 500-503. Habl, G., A. Schmitt, M. Zink, M. von Wilmsdorff, P. Yeganeh-Doost, A. Jatzko, T. Schneider-Axmann, M. Bauer and P. Falkai (2012). "Decreased reelin expression in the left prefrontal cortex (BA9) in chronic schizophrenia patients." Neuropsychobiology 66(1): 57-62. Hamburgh, M. (1963). "ANALYSIS OF THE POSTNATAL DEVELOPMENTAL EFFECTS OF "REELER," A NEUROLOGICAL MUTATION IN MICE. A STUDY IN DEVELOPMENTAL GENETICS." Dev Biol 8: 165-185. Hamers-Casterman, C., T. Atarhouch, S. Muyldermans, G. Robinson, C. Hamers, E. B. Songa, N. Bendahman and R. Hamers (1993). "Naturally occurring antibodies devoid of light chains." Nature 363(6428): 446-448. Harmsen, M. M., R. C. Ruuls, I. J. Nijman, T. A. Niewold, L. G. Frenken and B. de Geus (2000). "Llama heavy-chain V regions consist of at least four distinct subfamilies revealing novel sequence features." Mol Immunol 37(10): 579-590. Heinrich, C., N. Nitta, A. Flubacher, M. Muller, A. Fahrner, M. Kirsch, T. Freiman, F. Suzuki, A. Depaulis, M. Frotscher and C. A. Haas (2006). "Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus." J Neurosci 26(17): 4701-4713. Hellmert, M., A. Muller-Schiffmann, M. S. Peters, C. Korth and T. Schrader (2015). "Hybridization of an Abeta-specific antibody fragment with aminopyrazole-based beta-sheet ligands displays striking enhancement of target affinity." Org Biomol Chem 13(10): 2974-2979. Herz, J. and Y. Chen (2006). "Reelin, lipoprotein receptors and synaptic plasticity." Nat Rev Neurosci 7(11): 850-859. Hiesberger, T., M. Trommsdorff, B. W. Howell, A. Goffinet, M. C. Mumby, J. A. Cooper and J. Herz (1999). "Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation." Neuron 24(2): 481-489. Hirotsune, S., T. Takahara, N. Sasaki, K. Hirose, A. Yoshiki, T. Ohashi, M. Kusakabe, Y. Murakami, M. Muramatsu, S. Watanabe and et al. (1995). "The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons." Nat Genet 10(1): 77-83. Hof, H., Dörries, R. (2000, 2009). Medizinische Mikrobiologie. Stuttgart, Georg Thieme Verlag KG. Hong, S. E., Y. Y. Shugart, D. T. Huang, S. A. Shahwan, P. E. Grant, J. O. Hourihane, N. D. Martin and C. A. Walsh (2000). "Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations." Nat Genet 26(1): 93-96. Hornig, T., C. Haas, L. Sturm, B. Fiebich and L. Tebartz van Elst (2015). "Increased Blood-Reelin-Levels in First Episode Schizophrenia." PLoS One 10(8): e0134671. Hourihane, J. O., C. P. Bennett, R. Chaudhuri, S. A. Robb and N. D. Martin (1993). "A sibship with a neuronal migration defect, cerebellar hypoplasia and congenital lymphedema." Neuropediatrics 24(1): 43-46. Houser, C. R. (1990). "Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy." Brain Res 535(2): 195-204. Howell, B. W., T. M. Herrick and J. A. Cooper (1999). "Reelin-induced tyrosine [corrected] phosphorylation of disabled 1 during neuronal positioning." Genes Dev 13(6): 643-648. Howell, B. W., T. M. Herrick, J. D. Hildebrand, Y. Zhang and J. A. Cooper (2000). "Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development." Curr Biol 10(15): 877-885. Ignatova, N., C. J. Sindic and A. M. Goffinet (2004). "Characterization of the various forms of the Reelin protein in the cerebrospinal fluid of normal subjects and in neurological diseases." Neurobiol Dis 15(2): 326-330. IMGSAC (1998). "A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium." Hum Mol Genet 7(3): 571-578. Impagnatiello, F., A. R. Guidotti, C. Pesold, Y. Dwivedi, H. Caruncho, M. G. Pisu, D. P. Uzunov, N. R. Smalheiser, J. M. Davis, G. N. Pandey, G. D. Pappas, P. Tueting, R. P. Sharma and E. Costa (1998). "A decrease of reelin expression as a putative vulnerability factor in schizophrenia." Proc Natl Acad Sci U S A 95(26): 15718-15723. Iwata, K., N. Izumo, H. Matsuzaki, T. Manabe, Y. Ishibashi, Y. Ichitani, K. Yamada, I. Thanseem, A. Anitha, M. M. Vasu, C. Shimmura, T. Wakuda, Y. Kameno, T. Takahashi, Y. Iwata, K. Suzuki, K. Nakamura and N. Mori (2012). "Vldlr overexpression causes hyperactivity in rats." Mol Autism 3(1): 11. Jossin, Y., N. Ignatova, T. Hiesberger, J. Herz, C. Lambert de Rouvroit and A. M. Goffinet (2004). "The central fragment of Reelin, generated by proteolytic processing in vivo, is critical to its function during cortical plate development." J Neurosci 24(2): 514-521. Kabat, E. A. and T. T. Wu (1991). "Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites." J Immunol 147(5): 1709-1719. Kearney, J. F., A. Radbruch, B. Liesegang and K. Rajewsky (1979). "A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines." J Immunol 123(4): 1548-1550. Keshvara, L., D. Benhayon, S. Magdaleno and T. Curran (2001). "Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1." J Biol Chem 276(19): 16008-16014. Klar, A., M. Baldassare and T. M. Jessell (1992). "F-spondin: a gene expressed at high levels in the floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension." Cell 69(1): 95-110. Knoll, B., C. Weinl, A. Nordheim and F. Bonhoeffer (2007). "Stripe assay to examine axonal guidance and cell migration." Nat Protoc 2(5): 1216-1224. Knuesel, I., M. Nyffeler, C. Mormede, M. Muhia, U. Meyer, S. Pietropaolo, B. K. Yee, C. R. Pryce, F. M. LaFerla, A. Marighetto and J. Feldon (2009). "Age-related accumulation of Reelin in amyloid-like deposits." Neurobiol Aging 30(5): 697-716. Kocherhans, S., A. Madhusudan, J. Doehner, K. S. Breu, R. M. Nitsch, J. M. Fritschy and I. Knuesel (2010). "Reduced Reelin expression accelerates amyloid-beta plaque formation and tau pathology in transgenic Alzheimer's disease mice." J Neurosci 30(27): 9228-9240. Kohler, G. and C. Milstein (1975). "Continuous cultures of fused cells secreting antibody of predefined specificity." Nature 256(5517): 495-497. Kramer, P. L., H. Xu, R. L. Woltjer, S. K. Westaway, D. Clark, D. Erten-Lyons, J. A. Kaye, K. A. Welsh-Bohmer, J. C. Troncoso, W. R. Markesbery, R. C. Petersen, R. S. Turner, W. A. Kukull, D. A. Bennett, D. Galasko, J. C. Morris and J. Ott (2011). "Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study." Neurobiol Aging 32(12): 2113-2122. Krebs, M. O., C. Betancur, S. Leroy, M. C. Bourdel, C. Gillberg and M. Leboyer (2002). "Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism." Mol Psychiatry 7(7): 801-804. Kubo, K., K. Mikoshiba and K. Nakajima (2002). "Secreted Reelin molecules form homodimers." Neurosci Res 43(4): 381-388. Lambert de Rouvroit, C., V. de Bergeyck, C. Cortvrindt, I. Bar, Y. Eeckhout and A. M. Goffinet (1999). "Reelin, the extracellular matrix protein deficient in reeler mutant mice, is processed by a metalloproteinase." Exp Neurol 156(1): 214-217. Lammert, D. B. and B. W. Howell (2016). "RELN Mutations in Autism Spectrum Disorder." Front Cell Neurosci 10: 84. Lauwereys, M., M. Arbabi Ghahroudi, A. Desmyter, J. Kinne, W. Holzer, E. De Genst, L. Wyns and S. Muyldermans (1998). "Potent enzyme inhibitors derived from dromedary heavy-chain antibodies." Embo j 17(13): 3512-3520. Li, J., J. Liu, L. Zhao, Y. Ma, M. Jia, T. Lu, Y. Ruan, Q. Li, W. Yue, D. Zhang and L. Wang (2013). "Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population." Prog Neuropsychopharmacol Biol Psychiatry 44: 226-232. Liu, W. S., C. Pesold, M. A. Rodriguez, G. Carboni, J. Auta, P. Lacor, J. Larson, B. G. Condie, A. Guidotti and E. Costa (2001). "Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse." Proc Natl Acad Sci U S A 98(6): 3477-3482. Makrides, S. C. (1996). "Strategies for achieving high-level expression of genes in Escherichia coli." Microbiol Rev 60(3): 512-538. Manford, M., Y. M. Hart, J. W. Sander and S. D. Shorvon (1992). "National General Practice Study of Epilepsy (NGPSE): partial seizure patterns in a general population." Neurology 42(10): 1911-1917. Mariani, J., F. Crepel, K. Mikoshiba, J. P. Changeux and C. Sotelo (1977). "Anatomical, physiological and biochemical studies of the cerebellum from Reeler mutant mouse." Philos Trans R Soc Lond B Biol Sci 281(978): 1-28. Maurizi, M. R. (1992). "Proteases and protein degradation in Escherichia coli." Experientia 48(2): 178-201. Mayer, H., S. Duit, C. Hauser, W. J. Schneider and J. Nimpf (2006). "Reconstitution of the Reelin signaling pathway in fibroblasts demonstrates that Dab1 phosphorylation is independent of receptor localization in lipid rafts." Mol Cell Biol 26(1): 19-27. Michelucci, R., P. Pulitano, C. Di Bonaventura, S. Binelli, C. Luisi, E. Pasini, S. Striano, P. Striano, G. Coppola, A. La Neve, A. T. Giallonardo, O. Mecarelli, E. Serioli, E. Dazzo, M. Fanciulli and C. Nobile (2017). "The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations." Epilepsy Behav 68: 103-107. Miles, J. H. (2011). "Autism spectrum disorders--a genetics review." Genet Med 13(4): 278-294. Millar, J. K., J. C. Wilson-Annan, S. Anderson, S. Christie, M. S. Taylor, C. A. Semple, R. S. Devon, D. M. St Clair, W. J. Muir, D. H. Blackwood and D. J. Porteous (2000). "Disruption of two novel genes by a translocation co-segregating with schizophrenia." Hum Mol Genet 9(9): 1415-1423. Missiakas, D. and S. Raina (1997). "Protein folding in the bacterial periplasm." J Bacteriol 179(8): 2465-2471. Moy, S. S. and J. J. Nadler (2008). "Advances in behavioral genetics: mouse models of autism." Mol Psychiatry 13(1): 4-26. Muyldermans, S. (2001). "Single domain camel antibodies: current status." J Biotechnol 74(4): 277-302. Muyldermans, S., T. Atarhouch, J. Saldanha, J. A. Barbosa and R. Hamers (1994). "Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains." Protein Eng 7(9): 1129-1135. Muyldermans, S., T. N. Baral, V. C. Retamozzo, P. De Baetselier, E. De Genst, J. Kinne, H. Leonhardt, S. Magez, V. K. Nguyen, H. Revets, U. Rothbauer, B. Stijlemans, S. Tillib, U. Wernery, L. Wyns, G. Hassanzadeh-Ghassabeh and D. Saerens (2009). "Camelid immunoglobulins and nanobody technology." Vet Immunol Immunopathol 128(1-3): 178-183. Neurologie, K. L. d. d. G. f. (30.04.2017, 30.04.2017). "Leitlinien für Diagnostik und Therapie in der Neurologie, Erster epileptischer Anfall und Epilepsien im Erwachsenenalter." Retrieved 06.07.2017, from http://www.awmf.org/uploads/tx_szleitlinien/030-041l_S1_Erster-epileptischer-Anfall_Epilespien_2017-05.pdf. Nguyen, V. K., R. Hamers, L. Wyns and S. Muyldermans (1999). "Loss of splice consensus signal is responsible for the removal of the entire C(H)1 domain of the functional camel IGG2A heavy-chain antibodies." Mol Immunol 36(8): 515-524. Nguyen, V. K., R. Hamers, L. Wyns and S. Muyldermans (2000). "Camel heavy-chain antibodies: diverse germline V(H)H and specific mechanisms enlarge the antigen-binding repertoire." Embo j 19(5): 921-930. Niu, S., A. Renfro, C. C. Quattrocchi, M. Sheldon and G. D'Arcangelo (2004). "Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway." Neuron 41(1): 71-84. Ogawa, M., T. Miyata, K. Nakajima, K. Yagyu, M. Seike, K. Ikenaka, H. Yamamoto and K. Mikoshiba (1995). "The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons." Neuron 14(5): 899-912. Okamura, Y., S. Nomoto, M. Kanda, M. Hayashi, Y. Nishikawa, T. Fujii, H. Sugimoto, S. Takeda and A. Nakao (2011). "Reduced expression of reelin (RELN) gene is associated with high recurrence rate of hepatocellular carcinoma." Ann Surg Oncol 18(2): 572-579. Orcinha, C., G. Munzner, J. Gerlach, A. Kilias, M. Follo, U. Egert and C. A. Haas (2016). "Seizure-Induced Motility of Differentiated Dentate Granule Cells Is Prevented by the Central Reelin Fragment." Front Cell Neurosci 10: 183. Palladino, G., V. Nicolia, G. G. Kovacs, S. Canterini, V. Ciraci, A. Fuso, F. Mangia, S. Scarpa and M. T. Fiorenza (2017). "Sexually Dimorphic Expression of Reelin in the Brain of a Mouse Model of Alzheimer Disease." J Mol Neurosci 61(3): 359-367. Pappas, G. D., V. Kriho and C. Pesold (2001). "Reelin in the extracellular matrix and dendritic spines of the cortex and hippocampus: a comparison between wild type and heterozygous reeler mice by immunoelectron microscopy." J Neurocytol 30(5): 413-425. Perez, J. M., J. G. Renisio, J. J. Prompers, C. J. van Platerink, C. Cambillau, H. Darbon and L. G. Frenken (2001). "Thermal unfolding of a llama antibody fragment: a two-state reversible process." Biochemistry 40(1): 74-83. Persico, A. M., L. D'Agruma, N. Maiorano, A. Totaro, R. Militerni, C. Bravaccio, T. H. Wassink, C. Schneider, R. Melmed, S. Trillo, F. Montecchi, M. Palermo, T. Pascucci, S. Puglisi-Allegra, K. L. Reichelt, M. Conciatori, R. Marino, C. C. Quattrocchi, A. Baldi, L. Zelante, P. Gasparini and F. Keller (2001). "Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder." Mol Psychiatry 6(2): 150-159. Persico, A. M. and V. Napolioni (2013). "Autism genetics." Behav Brain Res 251: 95-112. Pesold, C., F. Impagnatiello, M. G. Pisu, D. P. Uzunov, E. Costa, A. Guidotti and H. J. Caruncho (1998). "Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats." Proc Natl Acad Sci U S A 95(6): 3221-3226. Peters, J. H. B., H. (1990). Monoklonale Antikörper: Herstellung und Charakterisierung. Heidelberg, Springer Verlag. Pujadas, L., A. Gruart, C. Bosch, L. Delgado, C. M. Teixeira, D. Rossi, L. de Lecea, A. Martinez, J. M. Delgado-Garcia and E. Soriano (2010). "Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long-term potentiation." J Neurosci 30(13): 4636-4649. Pujadas, L., D. Rossi, R. Andres, C. M. Teixeira, B. Serra-Vidal, A. Parcerisas, R. Maldonado, E. Giralt, N. Carulla and E. Soriano (2014). "Reelin delays amyloid-beta fibril formation and rescues cognitive deficits in a model of Alzheimer's disease." Nat Commun 5: 3443. Rakic, P. (1972). "Mode of cell migration to the superficial layers of fetal monkey neocortex." J Comp Neurol 145(1): 61-83. Rakic, P. (1988). "Specification of cerebral cortical areas." Science 241(4862): 170-176. Rakic, P. and V. S. Caviness, Jr. (1995). "Cortical development: view from neurological mutants two decades later." Neuron 14(6): 1101-1104. Rossky, P. J. (2008). "Protein denaturation by urea: slash and bond." Proc Natl Acad Sci U S A 105(44): 16825-16826. Saez-Valero, J., M. Costell, M. Sjogren, N. Andreasen, K. Blennow and J. M. Luque (2003). "Altered levels of cerebrospinal fluid reelin in frontotemporal dementia and Alzheimer's disease." J Neurosci Res 72(1): 132-136. Schneider, F. (2017). Facharztwissen Psychiatrie, Psychosomatik und Psychotherapie, Springer Verlag. Seligmann, M., E. Mihaesco, J. L. Preud'homme, F. Danon and J. C. Brouet (1979). "Heavy chain diseases: current findings and concepts." Immunol Rev 48: 145-167. Shen, Y., G. Xun, H. Guo, Y. He, J. Ou, H. Dong, K. Xia and J. Zhao (2016). "Association and gene-gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population." Autism Res 9(4): 436-442. Stanfield, B. B. and W. M. Cowan (1979). "The morphology of the hippocampus and dentate gyrus in normal and reeler mice." J Comp Neurol 185(3): 393-422. Talmadge, K. and W. Gilbert (1982). "Cellular location affects protein stability in Escherichia coli." Proc Natl Acad Sci U S A 79(6): 1830-1833. Transue, T. R., E. De Genst, M. A. Ghahroudi, L. Wyns and S. Muyldermans (1998). "Camel single-domain antibody inhibits enzyme by mimicking carbohydrate substrate." Proteins 32(4): 515-522. Trommsdorff, M., M. Gotthardt, T. Hiesberger, J. Shelton, W. Stockinger, J. Nimpf, R. E. Hammer, J. A. Richardson and J. Herz (1999). "Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2." Cell 97(6): 689-701. Tseng, W. L., C. L. Huang, K. Y. Chong, C. H. Liao, A. Stern, J. C. Cheng and C. P. Tseng (2010). "Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen." Cell Mol Life Sci 67(4): 641-653. Tueting, P., E. Costa, Y. Dwivedi, A. Guidotti, F. Impagnatiello, R. Manev and C. Pesold (1999). "The phenotypic characteristics of heterozygous reeler mouse." Neuroreport 10(6): 1329-1334. Underhill, G. H., D. George, E. G. Bremer and G. S. Kansas (2003). "Gene expression profiling reveals a highly specialized genetic program of plasma cells." Blood 101(10): 4013-4021. Utsunomiya-Tate, N., K. Kubo, S. Tate, M. Kainosho, E. Katayama, K. Nakajima and K. Mikoshiba (2000). "Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody." Proc Natl Acad Sci U S A 97(17): 9729-9734. Vu, K. B., M. A. Ghahroudi, L. Wyns and S. Muyldermans (1997). "Comparison of llama VH sequences from conventional and heavy chain antibodies." Mol Immunol 34(16-17): 1121-1131. Wang, Z., Y. Hong, L. Zou, R. Zhong, B. Zhu, N. Shen, W. Chen, J. Lou, J. Ke, T. Zhang, W. Wang and X. Miao (2014). "Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis." Am J Med Genet B Neuropsychiatr Genet 165b(2): 192-200. Wasser, C. R. and J. Herz (2017). "Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses." J Biol Chem 292(4): 1330-1338. Weeber, E. J., U. Beffert, C. Jones, J. M. Christian, E. Forster, J. D. Sweatt and J. Herz (2002). "Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning." J Biol Chem 277(42): 39944-39952. Woolven, B. P., L. G. Frenken, P. van der Logt and P. J. Nicholls (1999). "The structure of the llama heavy chain constant genes reveals a mechanism for heavy-chain antibody formation." Immunogenetics 50(1-2): 98-101. Wu, T. T., G. Johnson and E. A. Kabat (1993). "Length distribution of CDRH3 in antibodies." Proteins 16(1): 1-7. Zhang, H., X. Liu, C. Zhang, E. Mundo, F. Macciardi, D. R. Grayson, A. R. Guidotti and J. J. Holden (2002). "Reelin gene alleles and susceptibility to autism spectrum disorders." Mol Psychiatry 7(9): 1012-1017. Zola, H., A. P. Mohandas and D. Krumbiegel (2001). Monoclonal Antibodies: Diagnostic Uses. eLS, John Wiley & Sons, Ltd. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Neuropathologie | |||||||
| Dokument erstellt am: | 21.04.2021 | |||||||
| Dateien geändert am: | 21.04.2021 | |||||||
| Promotionsantrag am: | 22.10.2019 | |||||||
| Datum der Promotion: | 13.04.2021 |
