A Mouse Model of Duodenal Mucosal Resurfacing – UROP Symposium

A Mouse Model of Duodenal Mucosal Resurfacing

Garrett McMahon

Pronouns: He/Him

Research Mentor(s): Nadejda Bozadjieva Kramer
Research Mentor School/College/Department: Surgery / Medicine
Program:
Authors: Garrett McMahon, Andriy Myronovych, Neil Blok, Randy Seeley, Nadejda Bozadjieva Kramer
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 42

Abstract

Type 2 diabetes (T2D) is a health issue that is increasing in prevalence globally. T2D is defined by abnormal glycemic control. Medications can improve glycemic control in patients with T2D, but such medications must be taken for the duration of the patient’s life. Duodenal mucosal resurfacing (DMR) is an experimental procedure that temporarily ablates the duodenal mucosal surface and has been shown to durably mitigate the negative metabolic effects of T2D. However, the mechanisms behind this success are unknown. We developed a mouse model of this procedure by engineering mice to express the diphtheria toxin receptor (which is not normally present in mice) in their intestinal mucosal cells. The diphtheria toxin thus ablates cells that express the receptor. In this experiment, we observed a cohort of mice that was evenly split between an experimental group that expressed the diphtheria toxin receptor, and a control group that did not. Obesity was induced in the entire cohort via a high-fat diet. After 9 weeks, the diphtheria toxin was applied. We measured the change in body mass, fat mass, lean mass for 5 weeks post treatment, and performed a mixed meal glucose tolerance test 2 weeks post treatment to assess whether the mouse model was effective.

Interdisciplinary, Natural/Life Sciences

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