Impaired APP activity and altered Tau splicing in embryonic stem cell-derived astrocytes obtained from an APPsw transgenic minipig

DMM Disease Models and Mechanisms

Volumn 8, Issue 10, 2015, Pages 1265-1278

  Hall, Vanessa J ^a   Lindblad, Maiken M ^a   Jakobsen, Jannik E ^b   Gunnarsson, Anders ^b   Schmidt, Mette ^c   Rasmussen, Mikkel A ^d   Volke, Daniela ^e   Zuchner, Thole ^f   Hyttel, Poul ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b AARHUS UNIVERSITY   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

^d BIONEER A S   (Denmark)

^e UNIVERSITY OF LEIPZIG   (Germany)

^f Octapharma Biopharmaceuticals GmbH   (Germany)

Author keywords

Alzheimer's disease; APP Swedish mutation; Astrocytes; Astrogenesis; Cell cycle; Pig; Radial glial cells; Secretase expression; Tau phosphorylation

Indexed keywords

ALPHA SECRETASE; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; CELL MARKER; CYCLIN D1; GAMMA SECRETASE; GLIAL FIBRILLARY ACIDIC PROTEIN; NESTIN; NOTCH1 RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN BLBP; RIBOSOME RNA; TAU PROTEIN; TRANSCRIPTION FACTOR SOX2; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; SECRETASE;

ANIMAL CELL; ANIMAL MODEL; ARTICLE; ASTROCYTE; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL RENEWAL; CONTROLLED STUDY; EMBRYO; EMBRYONIC STEM CELL; ENZYME ACTIVITY; FETUS; FIBROBLAST; GENE MUTATION; GENE OVEREXPRESSION; GENOTYPE; HEMIZYGOTE; HOMOZYGOTE; IN VITRO STUDY; MACROGLIA; MINIPIG; NONHUMAN; PIG; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RNA GENE; RNA SYNTHESIS; SIGNAL TRANSDUCTION; SPLICING DEFECT; TRANSGENIC ANIMAL; TRANSGENIC MINIPIG; ANIMAL; BIOSYNTHESIS; CYTOLOGY; GENETICS; GLIA; HUMAN; METABOLISM; MUTATION; NERVOUS SYSTEM DEVELOPMENT; PHOSPHORYLATION; RNA SPLICING;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ANIMALS, GENETICALLY MODIFIED; ASTROCYTES; CELL DIFFERENTIATION; EMBRYONIC STEM CELLS; HUMANS; MUTATION; NEUROGENESIS; NEUROGLIA; PHOSPHORYLATION; RNA SPLICING; RNA, RIBOSOMAL; SIGNAL TRANSDUCTION; SWINE; SWINE, MINIATURE; TAU PROTEINS;

EID: 84943379725     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.019489     Document Type: Article

References (61)

1. Aigner, B., Renner, S., Kessler, B., Klymiuk, N., Kurome, M., Wunsch, A. and Wolf, E. (2010). Transgenic pigs as models for translational biomedical research. J. Mol. Med. 88, 653-664.
2. Bigl, M., Apelt, J., Luschekina, E. A., Lange-Dohna, C., Rossner, S. and Schliebs, R. (2000). Expression of beta-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology. Neurosci. Lett. 292, 107-110.
3. Bollineni, R. C., Hoffmann, R. and Fedorova, M. (2014). Proteome-wide profiling of carbonylated proteins and carbonylation sites in HeLa cells under mild oxidative stress conditions. Free Radic. Biol. Med. 68, 186-195.
4. Bondolfi, L., Calhoun, M., Ermini, F., Kuhn, H. G., and Wiederhold, K. H., Walker, L., Staufenbiel, M. and Jucker, M. (2002). Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J. Neurosci. 22, 515-522.
5. Cai, X. D., Golde, T. E. and Younkin, S. G. (1993). Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259, 514-516.
6. Citron, M., Vigo-Pelfrey, C., Teplow, D. B., Miller, C., Schenk, D., Johnston, J., Winblad, B., Venizelos, N., Lannfelt, L. and Selkoe, D. J. (1994). Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Natl. Acad. Sci. USA 91, 11993-11997.
7. Cohen, R. M., Rezai-Zadeh, K., Weitz, T. M., Rentsendorj, A., Gate, D., Spivak, I., Bholat, Y., Vasilevko, V., Glabe, C. G., Breunig, J. J. et al. (2013). A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric abeta, and frank neuronal loss. J. Neurosci. 33, 6245-6256.
8. da Silva, A. M. A., Payão, S. L. M., Borsatto, B., Bertolucci, P. H. F. and Smith, M. d. A. C. (2000). Quantitative evaluation of the rRNA in Alzheimer's disease. Mech. Ageing Dev. 120, 57-64.
9. Deguchi, T., Misawa, H. and Takahashi, R. (1994). Differentiation of cholinergic neurons and physiological role of ciliary neurotrophic factor (CNTF). J. Physiol. 88, 229-233.
10. Demars, M., Hu, Y.-S., Gadadhar, A. and Lazarov, O. (2010). Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J. Neurosci. Res. 88, 2103-2117.
11. Ding, Q., and Markesbery, W. R., Chen, Q., Li, F. and Keller, J. N. (2005). Ribosome dysfunction is an early event in Alzheimer's disease. J. Neurosci. 25, 9171-9175.
12. Dolezalova, D., Hruska-Plochan, M., Bjarkam, C. R., Sørensen, J. C. H., Cunningham, M., Weingarten, D., Ciacci, J. D., Juhas, S., Juhasova, J., Motlik, J. et al. (2014). Pig models of neurodegenerative disorders: utilization in cell replacement-based preclinical safety and efficacy studies. J. Comp. Neurol. 522, 2784-2801.
13. Donmez-Altuntas, H., Akalin, H., Karaman, Y., Demirtas, H., Imamoglu, N. and Ozkul, Y. (2005). Evaluation of the nucleolar organizer regions in Alzheimer's disease. Gerontology 51, 297-301.
14. Dubois-Dauphin, M. L., Toni, N., Julien, S. D., Charvet, I., Sundstrom, L. E. and Stoppini, L. (2010). The long-term survival of in vitro engineered nervous tissue derived from the specific neural differentiation of mouse embryonic stem cells. Biomaterials 31, 7032-7042.
15. Eder-Colli, L., Abad-Estarlich, N., Pannetier, C., and Vallet, P. G., Walzer, C., Elder, G. A., Robakis, N.K., Bouras, C. and Savioz, A. (2009). The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells. Brain Res. Bull. 80, 296-301.
16. Elder, G. A., Gama Sosa, M. A. and De Gasperi, R. (2010). Transgenic mouse models of Alzheimer's disease. Mount Sinai J. Med. 77, 69-81.
17. Faure, A., Verret, L., Bozon, B., El Tannir El Tayara, N., Ly, M., Kober, F., Dhenain, M., Rampon, C. and Delatour, B. (2011). Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease. Neurobiol. Aging 32, 407-418.
18. Folkesson, R., Malkiewicz, K., Kloskowska, E., Nilsson, T., Popova, E., Bogdanovic, N., Ganten, U., Ganten, D., Bader, M., Winblad, B. et al. (2007). A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation. Biochem. Biophys. Res. Commun. 358, 777-782.
19. Ghashghaei, H. T., Weber, J., Pevny, L., Schmid, R., and Schwab, M. H., Lloyd, K. C. K., Eisenstat, D. D., Lai, C. and Anton, E. S. (2006). The role of neuregulin-ErbB4 interactions on the proliferation and organization of cells in the subventricular zone. Proc. Natl. Acad. Sci. USA 103, 1930-1935.
20. Goedert, M. and Jakes, R. (1990). Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J. 9, 4225-4230.
21. He, P., Staufenbiel, M., Li, R. and Shen, Y. (2014). Deficiency of Patched 1-induced Gli1 signal transduction results in astrogenesis in Swedish mutated APP transgenic mice. Hum. Mol. Genet. 23, 6512-6527.
22. Hu, X., He, W., Luo, X., Tsubota, K. E. and Yan, R. (2013). BACE1 regulates hippocampal astrogenesis via the Jagged1-Notch pathway. Cell Rep. 4, 40-49.
23. Illenberger, S., Zheng-Fischhofer, Q., Preuss, U., Stamer, K., Baumann, K., Trinczek, B., Biernat, J., Godemann, R., Mandelkow, E.-M. and Mandelkow, E. (1998). The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells: implications for Alzheimer's disease. Mol. Biol. Cell 9, 1495-1512.
24. Irizarry, M. C., Soriano, F., McNamara, M., Page, K. J., Schenk, D., Games, D. and Hyman, B. T. (1997). Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 17, 7053-7059.
25. Iwatsubo, T., Hasegawa, M. and Ihara, Y. (1994). Neuronal and glial tau-positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. Acta Neuropathol. 88, 129-136.
26. Jakobsen, J. E., and Dantoft, T. M., Johansen, M. G. and Jørgensen, A. L. (2012). Expression pattern of a single transgene cassette located in endogenous GLIS3 of cloned pigs; a nested situation. Gene 502, 94-98.
27. Jelsing, J., and Olsen, A. K., Cumming, P., Gjedde, A., Hansen, A. K., Arnfred, S., Hemmingsen, R. and Pakkenberg, B. (2005). Avolumetric screening procedure for the Gottingen minipig brain. Exp. Brain Res. 162, 428-435.
28. Kamphuis, W., Middeldorp, J., Kooijman, L., Sluijs, J. A., Kooi, E.-J., Moeton, M., Freriks, M., Mizee, M. R. and Hol, E. M. (2014). Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease. Neurobiol. Aging 35, 492-510.
29. Kimura, N., Takahashi, M., Tashiro, T. and Terao, K. (2006). Amyloid β up-regulates brain-derived neurotrophic factor production from astrocytes: rescue from amyloid β-related neuritic degeneration. J. Neurosci. Res. 84, 782-789.
30. Kitazawa, M., Yamasaki, T. R. and LaFerla, F. M. (2004). Microglia as a potential bridge between the amyloid b-peptide and tau. Ann. N. Y. Acad. Sci. 1035, 85-103.
31. Kondo, T., Asai, M., Tsukita, K., Kutoku, Y., Ohsawa, Y., Sunada, Y., Imamura, K., Egawa, N., Yahata, N., Okita, K. et al. (2013). Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12, 487-496.
32. Kragh, P. M., and Nielsen, A. L., Li, J., Du, Y., Lin, L., Schmidt, M., Bøgh, I. B., Holm, I. E., Jakobsen, J. E., Johansen, M. G. et al. (2009). Hemizygous minipigs produced by random gene insertion and handmade cloning express the Alzheimer's disease-causing dominant mutation APPsw. Transgenic Res. 18, 545-558.
33. Lee, H., and Shamy, G. A., Elkabetz, Y., Schofield, C. M., and Harrsion, N. L., Panagiotakos, G., Socci, N. D., Tabar, V. and Studer, L. (2007). Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells 25, 1931-1939.
34. Lee, H.-G., Casadesus, G., Zhu, X., Castellani, R. J., McShea, A., Perry, G., Petersen, R. B., Bajic, V. and Smith, M. A. (2009). Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease. Neurochem. Int. 54, 84-88.
35. Li, X.-J. and Li, S. (2012). Influence of species differences on the neuropathology of transgenic Huntington's disease animal models. J. Genet. Genomics 39, 239-245.
36. Lopez-González, I., Carmona, M., Blanco, R., Luna-Muñoz, J., Martínez-Mandonado, A., Mena, R. and Ferrer, I. (2013). Characterization of thorn-shaped astrocytes in white matter of temporal lobe in Alzheimer's disease brains. Brain Pathol. 23, 144-153.
37. Luo, Y., Lin, L., Bolund, L., Jensen, T. G. and Sørensen, C. B. (2012). Genetically modified pigs for biomedical research. J. Inherit. Metab. Dis. 35, 695-713.
38. Madsen, L. B., Thomsen, B., Larsen, K., Bendixen, C., and Holm, I. E., Fredholm, M., Jørgensen, A. L. and Nielsen, A. L. (2007). Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain. BMC Neurosci. 8, 72.
39. Morrens, J., Van Den Broeck, W. and Kempermann, G. (2012). Glial cells in adult neurogenesis. Glia 60, 159-174.
40. Mrak, R. E. and Griffin, W. S. (1996). Role of activated glia and of glial cytokines in Alzheimer's disease: a review. EOS 16, 80-84.
41. Mu, Y. and Gage, F. H. (2011). Adult hippocampal neurogenesis and its role in Alzheimer's disease. Mol. Neurodegener. 6, 85.
42. Niwano, S. and Aizawa, Y. (1991). Fragmented atrial activity in patients with transient atrial fibrillation. Am. Heart J. 121, 62-67.
43. Nygard, A.-B., Jørgensen, C. B., Cirera, S. and Fredholm, M. (2007). Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR. BMC Mol. Biol. 8, 67.
44. Oddo, S., Caccamo, A., Shepherd, J. D., and Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., and Mattson, M. P., Akbari, Y. and LaFerla, F. M. (2003). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39, 409-421.
45. Payão, S. L. M., Smith, M. d. A. C., Winter, L. M. F. and Bertolucci, P. H. F. (1998). Ribosomal RNA in Alzheimer's disease and ageing. Mech. Ageing Dev. 105, 265-272.
46. Politis, P. K., Thomaidou, D. and Matsas, R. (2008). Coordination of cell cycle exit and differentiation of neuronal progenitors. Cell Cycle 7, 691-697.
47. Pons, S. and Marti, E. (2000). Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation. Development 127, 333-342.
48. Poulsen, H. E., Specht, E., Broedbaek, K., Henriksen, T., Ellervik, C., Mandrup-Poulsen, T., Tonnesen, M., and Nielsen, P. E., Andersen, H. U. and Weimann, A. (2012). RNA modificationsbyoxidation: a novel diseasemechanism? Free Radic. Biol. Med. 52, 1353-1361.
49. Preuss, U. and Mandelkow, E.-M. (1998). Mitotic phosphorylation of tau protein in neuronal cell lines resembles phosphorylation in Alzheimer's disease. Eur. J. Cell Biol. 76, 176-184.
50. Rasmussen, M. A., and Hall, V. J., Carter, T. F. and Hyttel, P. (2011). Directed differentiation of porcine epiblast-derived neural progenitor cells into neurons and glia. Stem Cell Res. 7, 124-136.
51. Reyes, J. F., and Reynolds, M. R., Horowitz, P. M., Fu, Y., Guillozet-Bongaarts, A. L., Berry, R. and Binder, L. I. (2008). A possible link between astrocyte activation and tau nitration in Alzheimer's disease. Neurobiol. Disord. 31, 198-208.
52. Rodríguez, J. J., Jones, V. C., Tabuchi, M., and Allan, S. M., Knight, E. M., LaFerla, F. M., Oddo, S. and Verkhratsky, A. (2008). Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease. PLoS ONE 3, e2935.
53. Rohrer, H. (1992). Cholinergic neuronal differentiation factors: evidence for the presence of both CNTF-like and non-CNTF-like factors in developing rat footpad. Development 114, 689-698.
54. Shan, X., Chang, Y. and Lin, C.-L. G. (2007). Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression. FASEB J. 21, 2753-2764.
55. Søndergaard, L. V., Ladewig, J., Dagnæs-Hansen, F., Herskin, M. S. and Holm, I. E. (2012). Object recognition as a measure of memory in 1-2 years old transgenic minipigs carrying the APPsw mutation for Alzheimer's disease. Transgenic Res. 21, 1341-1348.
56. Steiner, B., Klempin, F., Wang, L., Kott, M., Kettenmann, H. and Kempermann, G. (2006). Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis. Glia 54, 805-814.
57. Takeuchi, A., Irizarry, M.C., Duff, K., Saido, T.C., Hsiao Ashe, K., Hasegawa, M, Mann, D. M. A., Hyman, B. T. and Iwatsubo, T. (2000). Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss. Am. J. Pathol. 157, 331-339.
58. Thomsen, R., Sølvsten, C. A. E., Linnet, T. E., Blechingberg, J. and Nielsen, A. L. (2010). Analysis of qPCR data by converting exponentially related Ct values into linearly related X0 values. J. Bioinform. Comput. Biol. 8, 885-900.
59. Volke, D. and Hoffmann, R. (2006). Characterization of bovine tau-preparations by two-dimensional gel electrophoresis. Protein Pept. Lett. 13, 617-625.
60. Yang, D., Wang, C.-E., Zhao, B., Li, W., Ouyang, Z., Liu, Z., Yang, H., Fan, P., O'Neill, A., Gu, W. et al. (2010). Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs. Hum. Mol. Genet. 19, 3983-3994.
61. Zhao, J., O'Connor, T. and Vassar, R. (2011). The contribution of activated astrocytes to Abeta production: implications for Alzheimer's disease pathogenesis. J. Neuroinflamm. 8, 150.