A8-023287

Tamas Nagy, DVM, PhD

Department of PathologyCollege of Veterinary Medicine

University of Georgia

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

• 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

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A8-023287

• 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

A8-023287

Image courtesy of Dr. R. McManamonPresented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

Presented at SEVPAC 2008 – Permission granted for use on

SEVPAC website only

A8-023287

• 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

A8-023287• Discussion

– IL-10 (interleukin 10)• Member of the cytokine family (involved in

regulation of T lymphocyte activity)

• Produced by T regulatory lymphocytes, TH2 lymphocytes, and dendritic cells

• Important mediator in TH2-biased immunologic response – diffuse (lepromatous) granulomas

– Johne’s disease– Human leprosy– Crohn’s disease

Presented at SEVPAC 2008 – Permission granted for use on

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A8-023287• 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

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A8-023287• 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

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A8-023287• 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

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A8-023287• 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