Patterns of motor activity in the isolated large intestine of mice

Author: Kyra Barnes

Barnes, Kyra, 2016 Patterns of motor activity in the isolated large intestine of mice, Flinders University, School of Medicine

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The patterns of motor activity in the lower gastrointestinal tract of mammals and the mechanisms underlying their generation are incompletely understood. In this thesis, experiments were performed to provide greater insight into the role of the enteric nervous system in the generation of a cyclical propulsive motor pattern in the isolated mouse colon.

In Chapter 2, experiments revealed the importance of study design, and how motility patterns can change characteristics depending on the nature of the in vitro recording methods. Chapter 2 demonstrates that traditional recording methods for measuring colonic migrating motor complexes (CMMCs) in vitro can potently modify their frequency, velocity and extent of propagation. It is suggested that these altered properties are likely due to circumferential stretch and/or pinching (stimulation) of the colonic wall. Recording these motor patterns without using traditional in vitro techniques reveals that CMMC frequency and velocity is significantly lower from previously reported literature.

In Chapter 3, the characteristics of CMMCs were studied in a strain of mice that mimic the condition Hirschsprung’s disease in humans. These mice, named lethal spotted (ls/ls) mice lack the EDN3 gene, which is the same gene, when mutated in humans, that is directly responsible for the onset of colorectal aganglionosis and Hirschsprung’s disease. In our hands, when raised on a C57BL6 strain, these mice surprisingly had been found to predominantly live a normal lifespan, and are able to expel pellets without developing lethal megacolon. Interestingly it was found that CMMCs did occur in these mutant mice, and the length of the aganglionic segments were not as prominent as previously described by other laboratories which had used mice of a different strain of origin (where the mutation was fatal at a young age). We discuss the significance of the background strain of origin and length of aganglionosis in the lethality of the Hirschprung’s model mice.

The experiments conducted in this thesis have led to a greater insight into the mechanisms underlying colonic motility in mouse large intestine.

Keywords: colon, large intestine, motility, Hirschsprung's disease, mouse, aganglionic

Subject: Human Physiology thesis, Neuroscience thesis

Thesis type: Masters
Completed: 2016
School: School of Medicine
Supervisor: Professor Nicholas Spencer