Phenotypes Associated with This Genotype

Genotype
MGI:4429499

• Allelic Composition: Stat3^tm1Dlv/Stat3^tm1Dlv; Tg(Csf1r-icre)1Jwp/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body weight ( J:156593 )

• mutant mice that do not show symptoms of colitis have significantly lower body weights at older ages compared to controls

weight loss ( J:156593 )

• observed after colitis develops

digestive/alimentary system

diarrhea ( J:156593 )

• observed after colitis develops; animals produce bloody feces

abnormal intestinal mucosa morphology ( J:156593 )

• mice with or without evident colitis show increased intestinal mucosal thickening predominantly in the proximal colon

• significant decrease in goblet cell density in inflamed colon is observed compared to controls

abnormal cecum morphology ( J:156593 )

• visible polyps are found in inflamed areas of cecum

• herniation of colonic mucosa is observed in inflamed cecum

abnormal colon morphology ( J:156593 )

• mice with or without evident colitis show increased intestinal mucosal thickening predominantly in the proximal colon

• herniation of colonic mucosa is also observed in inflamed colon

• hyperplasia and dysplasia are also exhibited in inflamed intestinal tissue with over 60% of animals showing dysplasia between 8-39 weeks of age compared to no controls showing such phenotypes

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation in the colon and reduction in mucosal thickening compared to untreated mutants

• persistent proliferation of colonic epithelium in response to inflammation is observed compared to controls, with no difference in level of cell death

• colonic epithelial differentiation is perturbed in inflamed region

colon polyps ( J:156593 )

• visible polyps are found in inflamed areas of proximal colon and cecum

• most lesions are 'flat' with a broad base or are morphologically similar to 'dysplasia-associated lesions or masses'

• polyps/lesions are tumorous

increased gastrointestinal tumor incidence ( J:156593 )

• tumors develop in proximal colon and cecum

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation and tumor development in the colon; no tumors are detected in treated animals 21-27 weeks of age

colitis ( J:156593 )

• about 20% of animals develop pronounced colitis at 8 weeks of age; by 18-20 weeks, around 50% of animals develop colitis

immune system

increased granulocyte number ( J:156593 )

• moderately increased in proximal colon in mutants

increased T cell number ( J:156593 )

• significant increase in CD3+ T cells in proximal colon

increased macrophage cell number ( J:156593 )

• mutants have significantly higher density (number) of macrophages in the proximal colon

abnormal inflammatory response ( J:156593 )

• mice have higher leukocytic infiltration scores (degree of leukocytic infiltration and increased mucosal thickness) than controls

• almost all mutants develop inflammation of the colon compared to 1 control showing increased leukocytic infiltration; leukocytic infiltration score and infiltration of macrophages and T lymphocytes are reduced in treated mutants, but infiltrated macrophage number is still much higher than in controls

colitis ( J:156593 )

• about 20% of animals develop pronounced colitis at 8 weeks of age; by 18-20 weeks, around 50% of animals develop colitis

abnormal acute inflammation ( J:156593 )

• mice with or without evident colitis show increased leukocytic infiltration compared to controls

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation in the colon

hematopoietic system

increased granulocyte number ( J:156593 )

• moderately increased in proximal colon in mutants

increased T cell number ( J:156593 )

• significant increase in CD3+ T cells in proximal colon

increased macrophage cell number ( J:156593 )

• mutants have significantly higher density (number) of macrophages in the proximal colon

neoplasm

increased gastrointestinal tumor incidence ( J:156593 )

• tumors develop in proximal colon and cecum

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation and tumor development in the colon; no tumors are detected in treated animals 21-27 weeks of age

increased carcinoma incidence ( J:156593 )

• carcinoma is identified in some polyps (nodules) with invasion to submucosa or muscularis external; about 16% of mutants develop carcinoma

• presence of irregular or angulated glands with cell loss, desmoplasia and multiple invading mucosa are also observed

• cells in invasive glands exhibit severe atypia with pleomorphism and basement membrane loss

behavior/neurological

decreased locomotor activity ( J:156593 )

• mutant mice that do not show symptoms of colitis are less active at older ages compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:156593
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:156593