Transcriptional profiling of mRNA expression in the mouse distal colon.
OBJECTIVE
Intestinal epithelial cells and the myenteric plexus of the mouse gastrointestinal tract contain a circadian clock-based intrinsic time-keeping system. Because disruption of the biological clock has been associated with increased susceptibility to colon cancer and gastrointestinal symptoms, we aimed to identify rhythmically expressed genes in the mouse distal colon.


METHODS
Microarray analysis was used to identify genes that were rhythmically expressed over a 24-hour light/dark cycle. The transcripts were then classified according to expression pattern, function, and association with physiologic and pathophysiologic processes of the colon.


RESULTS
A circadian gene expression pattern was detected in approximately 3.7% of distal colonic genes. A large percentage of these genes were involved in cell signaling, differentiation, and proliferation and cell death. Of all the rhythmically expressed genes in the mouse colon, approximately 7% (64/906) have been associated with colorectal cancer formation (eg, B-cell leukemia/lymphoma-2 [Bcl2]) and 1.8% (18/906) with various colonic functions such as motility and secretion (eg, vasoactive intestinal polypeptide, cystic fibrosis transmembrane conductance regulator).


CONCLUSIONS
A subset of genes in the murine colon follows a rhythmic expression pattern. These findings may have significant implications for colonic physiology and pathophysiology.
Hoogerwerf
Willemijntje A
WA
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA. willemij@umich.edu
Sinha
Mala
M
Conesa
Ana
A
Luxon
Bruce A
BA
Shahinian
Vahakn B
VB
Cornélissen
Germaine
G
Halberg
Franz
F
Bostwick
Jonathon
J
Timm
John
J
Cassone
Vincent M
VM
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002940:Circadian Rhythm / Q000235:genetics*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D011506:Proteins; D012333:RNA, Messenger