Expression of RAD21 immunoreactivity in myenteric neurons of the human and mouse small intestine

F. Bianco, S. T. Eisenman, M. G. Colmenares Aguilar, E. Bonora, P. Clavenzani, D. R. Linden, R. De Giorgio, G. Farrugia, S. J. Gibbons

Research output: Contribution to journalArticle

Abstract

Background: RAD21 is a double-strand-break repair protein and component of the cohesin complex with key roles in cellular functions. A RAD21 loss-of-function mutation was found in cases of chronic intestinal pseudo-obstruction (CIPO) with associated enteric neuronal loss. Analysis of RAD21 expression in the enteric nervous system is lacking, thus we aimed to characterize RAD21 immunoreactivity (IR) in myenteric ganglia. Methods: Double labeling immunofluorescence in mouse and human jejunum was used to determine colocalization of RAD21 with HuC/D, PGP9.5, neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), choline acetyl transferase (ChAT), Kit, platelet-derived growth factor receptor-α (PDGFRα), and glial fibrillary acid protein (GFAP) IRs. Results: A subset of PGP9.5- and HuC/D-IR neuronal cell bodies and nerve fibers in the myenteric plexus of human and mouse small intestine also displayed cytoplasmic RAD21-IR Cytoplasmic RAD21-IR was found in 43% of HuC/D-IR neurons in adult and neonatal mice but did not colocalize with nNOS. A subset of ChAT-positive neurons had cytoplasmic RAD21-IR Punctate RAD21-IR was restricted to the nucleus in most cell types consistent with labeling of the cohesin complex. Cytoplasmic RAD21-IR was not detected in interstitial cells of Cajal, fibroblast-like cells or glia. Subsets of neurons in primary culture exhibited cytoplasmic RAD21-IR Suppression of RAD21 expression by shRNA knockdown abolished RAD21-IR in cultured neurons. Conclusions: Our data showing cytoplasmic RAD21 expression in enteric neurons provide a basis toward understanding how mutations of this gene may contribute to altered neuronal function/survival thus leading to gut-motor abnormalities.

Original languageEnglish (US)
Article numbere13429
JournalNeurogastroenterology and Motility
Volume30
Issue number9
DOIs
StatePublished - Sep 2018

Keywords

  • chronic intestinal pseudo-obstruction
  • enteric neurons
  • immunofluorescence

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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    Bianco, F., Eisenman, S. T., Colmenares Aguilar, M. G., Bonora, E., Clavenzani, P., Linden, D. R., De Giorgio, R., Farrugia, G., & Gibbons, S. J. (2018). Expression of RAD21 immunoreactivity in myenteric neurons of the human and mouse small intestine. Neurogastroenterology and Motility, 30(9), [e13429]. https://doi.org/10.1111/nmo.13429