A Tamas Nagy, DVM, PhD Department of Pathology College of Veterinary Medicine University of Georgia Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Signalment and history –3-month-old female IL-10 knock-out mouse –Kept in an individually ventilated microisolator cage with one other female and one male –Gave birth 7 days ago, but all the offspring died –No previous reproductive problems –Developed rectal prolapse 24 hours prior to euthanasia Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Gross pathology –Rectal prolapse –Gas-filled and moderately dilated proximal colon –Moderately thickened proximal colonic wall Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Image courtesy of Dr. R. McManamon Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Morphologic diagnosis –Colon: chronic, moderate, granulomatous colitis –Rectum: Rectal prolapse with secondary acute edema and serocellular crust formation Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Discussion –IL-10 (interleukin 10) Member of the cytokine family (involved in regulation of T lymphocyte activity) Produced by T regulatory lymphocytes, T H 2 lymphocytes, and dendritic cells Important mediator in T H 2-biased immunologic response – diffuse (lepromatous) granulomas –Johne’s disease –Human leprosy –Crohn’s disease Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Discussion – continued –IL-10 knock-out (IL-10 KO) mouse Created in 1993 Original report – IL-10 KO phenotype –Chronic enterocolitis in mice housed under conventional conditions –Colitis affecting only the proximal colon in mice housed under SPF conditions Model for human idiopathic inflammatory bowel diseases? Real cause: normal resident enteric bacteria especially in combination with Helicobacter hepaticus Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Differential diagnoses –Citrobacter rodentium infection Young mice or certain strains of mice affected (e.g. FVB) Sticky, unformed feces Rectal prolapse often occurs Brush border of the mucosa of the affected bowel is carpeted with attached cocco-bacilli Descending colon is affected Hyperplastic colonic mucosa with excessive numbers of goblet cells and leukocytic inflammation in the lamina propria Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Differential diagnoses – continued –Coliform typhlocolitis Atypical, non-lactose fermenting E. coli Intestinal lesions only occur in triple deficient mice (devoid of T, B, and NK cells) Segmental colonic hyperplasia with erosions and mononuclear inflammation –Helicobacter sp. induced proliferative typhlocolitis Immunodeficient (SCID & nude) mice Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

A Differential diagnoses – continued –Enterotropic MHV Neonatal mice in naïve mouse colonies Immunodeficient (SCID) mice Attenuated villi with syncytia formation (balloon cells) Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only