VCOM Research Day Program Book 2023

Medical Student Research Biomedical

33 HDAC6 Deletion Exacerbates DSS Induced Colitis in Mice

Joseph Spengler; Tonya LeRoith; Christopher Reilly; Dao Xu; Caitlin Armstrong; Michael Appiah Corresponding author: Jspengler@vt.vcom.edu

Edward Via College of Osteopathic Medicine-Virginia Campus Virginia-Maryland College of Veterinary Medicine

Inflammatory bowel disease (IBD) remains poorly understood largely due to its complex pathophysiology that results from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology remains undiscovered. However, it is widely accepted that IBD occurs when an inappropriately aggressive inflammatory response is mounted against a genetically susceptible host. To further investigate human IBD, various animal models have been developed providing indispensable insights into the pathogenesis of IBD leading to improvement in therapeutic options and patient outcomes. The most well-known experimental model employs dextran sodium sulfate (DSS) to induce colitis. Histone deacetylase 6 (HDAC6) inhibition has recently been reported to decrease DSS induced IBD. In our present studies, we aimed to determine the role that genetic deletion of HDAC6 had on DSS induced colitis in mice. Wild type (WT) and HDAC6

knockout (KO) mice were treated for 5 days with DSS dissolved in drinking water to induce colitis. Changes in weight, food and water intake, stool consistency, rectal bleeding, and colon length were assessed followed by histopathologic evaluation and immunofluorescence of colon tissues. Following DSS consumption body weights of both wild-type and HDAC6-/- mice decreased daily. However, no difference in weight change was observed between groups during the length of the experiment. HDAC6- /- mice developed a worse score for both fecal consistency and rectal bleeding, when compared to the wild-type. Furthermore, HDAC6-/- (KO) mice had longer colons, and the histological assessment of colon tissue further revealed a worse grade of colitis in KO mice. Further evaluation of colonic tissue of HDAC6-/- mice exhibited more severe features such as multifocal erosions, loss of crypts and glands, as well as suppurative inflammation that extended

transmurally. Our data indicates that deletion of HDAC6 exacerbates DSS-induced murine colitis. This suggests that genetic manipulation of HDAC6 is involved in the development of IBD and may be a candidate for inflammatory bowel disease treatment.

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