Morphological and functional abnormalities of hippocampus in APC1638T/1638T mice

Med Mol Morphol. 2021 Mar;54(1):31-40. doi: 10.1007/s00795-020-00257-3. Epub 2020 Jun 22.

Abstract

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.

Keywords: AMPA receptor; APC; APC1638T; Hippocampus; PSD-95.

MeSH terms

  • Adenomatous Polyposis Coli Protein / analysis
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Disks Large Homolog 4 Protein / analysis
  • Disks Large Homolog 4 Protein / metabolism
  • Hippocampus / pathology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Immunoelectron
  • Mutation
  • Receptors, AMPA / analysis
  • Receptors, AMPA / metabolism

Substances

  • Adenomatous Polyposis Coli Protein
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Receptors, AMPA
  • adenomatous polyposis coli protein, mouse