Clock Gene Expression in the Murine Gastrointestinal Tract

Endogenous Rhythmicity and Effects of a Feeding Regimen

Willemijntje A. Hoogerwerf, Helen Hellmich, Germaine Cornélissen, Franz Halberg, Vahakn B. Shahinian, Jonathon Bostwick, Tor C. Savidge, Vincent M. Cassone

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Background & Aims: Based on observations that the gastrointestinal tract is subject to various 24-hour rhythmic processes, it is conceivable that some of these rhythms are under circadian clock gene control. We hypothesized that clock genes are present in the gastrointestinal tract and that they are part of a functional molecular clock that coordinates rhythmic physiologic functions. Methods: The effects of timed feeding and vagotomy on temporal clock gene expression (clock, bmal1, per1-3, cry1-2) in the gastrointestinal tract and suprachiasmatic nucleus (bmal, per2) of C57BL/6J mice were examined using real-time polymerase chain reaction and Western blotting (BMAL, PER2). Colonic clock gene localization was examined using immunohistochemistry (BMAL, PER1-2). Results: Clock immunoreactivity was observed in the myenteric plexus and epithelial crypt cells. Clock genes were expressed rhythmically throughout the gastrointestinal tract. Timed feeding shifted clock gene expression at the RNA and protein level but did not shift clock gene expression in the central clock. Vagotomy did not alter gastric clock gene expression compared with sham-treated controls. Conclusions: The murine gastrointestinal tract contains functional clock genes, which are molecular core components of the circadian clock. Daytime feeding in nocturnal rodents is a strong synchronizer of gastrointestinal clock genes. This synchronization occurs independently of the central clock. Gastric clock gene expression is not mediated through the vagal nerve. The presence of clock genes in the myenteric plexus and epithelial cells suggests a role for clock genes in circadian coordination of gastrointestinal functions such as motility, cell proliferation, and migration.

Original languageEnglish (US)
Pages (from-to)1250-1260
Number of pages11
JournalGastroenterology
Volume133
Issue number4
DOIs
StatePublished - Oct 2007

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Periodicity
Gastrointestinal Tract
Gene Expression
Genes
Myenteric Plexus
Circadian Clocks
Vagotomy
Stomach
Epithelial Cells
Suprachiasmatic Nucleus
Inbred C57BL Mouse
Cell Movement
Real-Time Polymerase Chain Reaction
Rodentia
Western Blotting
Immunohistochemistry
Cell Proliferation
RNA

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Hoogerwerf, W. A., Hellmich, H., Cornélissen, G., Halberg, F., Shahinian, V. B., Bostwick, J., ... Cassone, V. M. (2007). Clock Gene Expression in the Murine Gastrointestinal Tract: Endogenous Rhythmicity and Effects of a Feeding Regimen. Gastroenterology, 133(4), 1250-1260. https://doi.org/10.1053/j.gastro.2007.07.009

Clock Gene Expression in the Murine Gastrointestinal Tract : Endogenous Rhythmicity and Effects of a Feeding Regimen. / Hoogerwerf, Willemijntje A.; Hellmich, Helen; Cornélissen, Germaine; Halberg, Franz; Shahinian, Vahakn B.; Bostwick, Jonathon; Savidge, Tor C.; Cassone, Vincent M.

In: Gastroenterology, Vol. 133, No. 4, 10.2007, p. 1250-1260.

Research output: Contribution to journalArticle

Hoogerwerf, WA, Hellmich, H, Cornélissen, G, Halberg, F, Shahinian, VB, Bostwick, J, Savidge, TC & Cassone, VM 2007, 'Clock Gene Expression in the Murine Gastrointestinal Tract: Endogenous Rhythmicity and Effects of a Feeding Regimen', Gastroenterology, vol. 133, no. 4, pp. 1250-1260. https://doi.org/10.1053/j.gastro.2007.07.009
Hoogerwerf, Willemijntje A. ; Hellmich, Helen ; Cornélissen, Germaine ; Halberg, Franz ; Shahinian, Vahakn B. ; Bostwick, Jonathon ; Savidge, Tor C. ; Cassone, Vincent M. / Clock Gene Expression in the Murine Gastrointestinal Tract : Endogenous Rhythmicity and Effects of a Feeding Regimen. In: Gastroenterology. 2007 ; Vol. 133, No. 4. pp. 1250-1260.
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