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Updated: May 21, 2026
Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice
Published on: February 3, 2016
Intestinal smooth muscle dysfunction develops postnatally in cystic fibrosis mice
Robert C De Lisle1, Lauren Meldi, Racquel Mueller
1University of Kansas School of Medicine, Anatomy and Cell Biology, Kansas City, KS 66160, USA. rdelisle@kumc.edu
Objectives:
Intestinal dysmotility is one of the effects of cystic fibrosis (CF), but when and how this develops is not well understood. The goal of the present study was to use the Cftr knockout mouse to determine when in development circular smooth muscle of the small intestine becomes dysfunctional.
Methods:
Wild-type (WT) and CF mice were used at postnatal day 5 (P5) through adult. Pieces of small intestine were used to measure contractile activity of the circular muscle. Bacterial overgrowth was measured by quantitative polymerase chain reaction (PCR) of the bacterial 16S gene. Intestinal gene expression was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Prostaglandin E2 (PGE2) and its metabolites were measured by enzyme immunoassay.
Results:
CF circular muscle response to cholinergic stimulation was similar to WT at P5, became somewhat impaired at P7, and was severely impaired by P14. In the CF intestine, bacterial overgrowth occurred by P4 and was maintained into adulthood. Eicosanoid metabolic gene expression in the CF intestine did not differ from WT shortly after birth. The phospholipase A2 genes, Pla2g4c and Pla2g5 exhibited increased expression in CF mice at P24. Prostaglandin degradative genes, Hpgd and Ptgr1, showed lower expression in CF as compared with WT at P16 and P24, respectively. PGE2 levels were significantly greater in CF mice at most ages from P7 through adulthood.
Conclusions:
The results clearly demonstrate that lack of CFTR itself does not cause smooth muscle dysfunction, because the circular muscle from P5 CF mice had normal activity and dysfunction developed between P7 and P14.
Insights
Cystic fibrosis (CF) intestinal smooth muscle dysfunction develops between postnatal days 7 and 14 in mice. This dysfunction is linked to bacterial overgrowth and altered prostaglandin E2 levels, not CFTR absence alone.
Area of Science:
- Gastroenterology
- Developmental Biology
- Genetics
Background:
- Intestinal dysmotility is a known complication of cystic fibrosis (CF).
- The precise developmental timing and mechanisms of CF-related intestinal smooth muscle dysfunction remain unclear.
- Understanding these factors is crucial for managing CF gastrointestinal complications.
Purpose of the Study:
- To determine the developmental onset of circular smooth muscle dysfunction in the small intestine of CF mice.
- To investigate the role of CFTR in the development of intestinal smooth muscle dysfunction.
Main Methods:
- Utilized wild-type (WT) and CFTR knockout (CF) mice from postnatal day 5 (P5) to adulthood.
- Assessed circular smooth muscle contractile activity in response to cholinergic stimulation.
- Quantified bacterial overgrowth using 16S rRNA gene quantitative PCR (qPCR).
- Analyzed intestinal gene expression via RT-qPCR and measured prostaglandin E2 (PGE2) levels using enzyme immunoassay.
Main Results:
- CF circular smooth muscle function was normal at P5 but impaired by P7 and severely dysfunctional by P14.
- Bacterial overgrowth was evident in CF intestines by P4 and persisted into adulthood.
- Increased expression of phospholipase A2 genes (Pla2g4c, Pla2g5) and elevated PGE2 levels were observed in CF mice from P7 onwards.
- Decreased expression of prostaglandin degradative genes (Hpgd, Ptgr1) was noted in CF mice at later time points.
Conclusions:
- CFTR absence itself does not directly cause smooth muscle dysfunction.
- Intestinal smooth muscle dysfunction in CF develops postnatally between P7 and P14.
- Bacterial overgrowth and altered eicosanoid metabolism likely contribute to the observed dysmotility.
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