In the present study, we examined morphology and function of hippocampus in the APC1638T/1638T mouse. Expression levels of the APC mRNA and protein were both identical in the hippocampus of the APC+/+ and APC1638T/1638T mice. The dentate gyrus of the APC1638T/1638T hippocampus was thicker, and has more densely-populated granule cells in the APC1638T/1638T mouse hippocampus. Immunoelectron microscopy revealed co-localization of APC with alpha-amino-3- hydroxy-5-methyl- isoxazole-4-propionate receptor (AMPA-R) and with PSD-95 at post-synapse in the APC+/+ hippocampus, while APC1638T was co-localized with neither AMPA-R nor PSD-95 in the APC1638T/1638T hippocampus. By immunoprecipitation assay, full-length APC expressed in the APC+/+ mouse was co-immunoprecipitated with AMPA-R and PSD-95. In contrast, APC1638T expressed in the APC1638T/1638T mouse was not co-immunoprecipitated with AMPA-R and PSD-95. In the hippocampal CA1 region of the APC1638T/1638T mouse, c-Fos expression after electric foot shock was decreased compared with the APC+/+ mouse. The present study showed some abnormalities on morphology of the hippocampus caused by a truncated APC (APC1638T). Also, our findings suggest that failure in APC binding to AMPA-R and PSD-95 may bring about less activities of hippocampal neurons in the APC1638T/1638T mouse.
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Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Boguski MS, Altschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y (1991) Identification of FAP locus genes from chromosome 5q21. Science 253(5020):661–665
Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, Mcphherson J, Wasmuth J, Paslier DL, Abderrahim H, Cohen D, Leppert M, White R (1991) Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66(3):589–600
Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253(5020):665–669
Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H (2001) Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 3(4):433–438
Senda T, Iizuka-Kogo A, Onouchi T, Shimomura A (2007) Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. Med Mol Morphol 40(2):68–81
Fodde R (2003) The multiple functions of tumour suppressors: it’s all in APC. Nat Cell Biol 5(3):190–192
Midgley CA, White S, Howitt R, Save V, Dunlop MG, Hall PA, Lane DP, Wyllie AH, Bubb VJ (1997) APC expression in normal human tissues. The Journal of pathology 181(4):426–433
Bhat RV, Baraban JM, Johnson RC, Eipper BA, Mains RE (1994) High levels of expression of the tumor suppressor gene APC during development of the rat central nervous system. J Neurosci 14(5 Pt 2):3059–3071
Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, Burger PC, Wood PA, Taqi F, Booker SV, Petersen GM, Offerhaus GJA, Tersmette AC, Giardiello FM, Vogelstein B, Kinzler KW (1995) The molecular basis of Turcot’s syndrome. N Engl J Med 332(13):839–847
Senda T, Iino S, Matsushita K, Matsumine A, Kobayashi S, Akiyama T (1998) Localization of the adenomatous polyposis coli tumour suppressor protein in the mouse central nervous system. Neuroscience 83(3):857–866
Shimomura A, Kohu K, Akiyama T, Senda T (2005) Subcellular localization of the tumor suppressor protein APC in developing cultured neurons. Neurosci Lett 375(2):81–86
Takamori N, Shimomura A, Senda T (2006) Microtubule-bundling activity of APC is stimulated by interaction with PSD-95. Neurosci Lett 403(1–2):68–72
Shimomura A, Ohkuma M, Iizuka-Kogo A, Kohu K, Nomura R, Miyachi E, Akiyama T, Senda T (2007) Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons. Eur J Neurosci 26(4):903–912
Smits R, Kielman MF, Breukel C, Zurcher C, Neufeld K, Jagmohan-Changur S, Hofland N, van Dijk J, White R, Edelmann W, Kucherlapati R, Khan PM, Fodde R (1999) Apc1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development. Genes Dev 13(10):1309–1321
Onouchi T, Kobayashi K, Sakai K, Shimomura A, Smits R, Sumi-Ichinose C, Kurosumi M, Takao K, Nomura R, Iizuka-Kogo A, Suzuki H, Kondo K, Akiyama T, Miyakawa T, Fodde R, Senda T (2014) Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia. Mol Brain 7:21
Schaeren-Wiemers N, Gerfin-Moser A (1993) A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes. Histochemistry 100(6):431–440
Nagano M, Adachi A, Masumoto KH, Meyer-Bernstein E, Shigeyoshi Y (2009) rPer1 and rPer2 induction during phases of the circadian cycle critical for light resetting of the circadian clock. Brain Res 1289:37–48
Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M (1995) Clustering of shaker-type K + channels by interaction with a family of membrane-associated guanylate kinases. Nature 378(6552):85–88
Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269(5231):1737–1740
Fleischmann A, Hvalby O, Jensen V, Strekalova T, Zacher C, Layer LE, Kvello A, Reschke M, Spanagel R, Sprengel R, Wagner EF, Gass P (2003) Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci 23(27):9116–9122
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132(4):645–660
Ehninger D, Kempermann (2008) Neurogenesisi in the adult hippocampus. Cell Tissue Res 331:243–250
Wang T, Onouchi T, Yamada NO, Matsuda S, Senda T (2017) A disturbance of intestinal epithelial cell population and kinetics in APC1638T mice. Med Mol Morphol 50(2):94–102
Munemitsu S, Souza B, Müller O, Albert I, Rubinfeld B, Polakis P (1994) The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res 54(14):3676–3681
Zumbrunn J, Kinoshita K, Hyman AA, Näthke IS (2001) Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 11(1):44–49
Tanaka EM, Kirschner MW (1991) Microtubule behavior in the growth cones of living neurons during axon elongation. The Journal of cell biology 115(2):345–363
We thank Prof. Yamaguchi (Gifu University) for technical advices, and Dr. Wenduerma (Gifu University) for technical assistance. This study was supported in part by grants-in aid for science research from the Ministry of Education, Science, Sports and Culture of Japan to T.S. (Grant No. 18K06827) and T.O. (Grant No. 18K14843), and from the Kazato Research Foundation to T.O.
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Li, C., Onouchi, T., Hirayama, M. et al. Morphological and functional abnormalities of hippocampus in APC1638T/1638T mice. Med Mol Morphol (2020). https://doi.org/10.1007/s00795-020-00257-3
- AMPA receptor