Phenotypes Associated with This Genotype

Genotype
MGI:5576251

• Allelic Composition: Nfil3^tm1Pbro/Nfil3^tm1Pbro
• Genetic Background: B6.129S6-Nfil3^tm1Pbro

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

immune system

colitis ( J:209365 )

• mice develop spontaneous chronic colitis that is Th1/Th7 mediated; colitis is variable and shows incomplete penetrance

• mice derived in a germ-free environment do not exhibit colitis at 6 months of age, however, upon transition from germ-free to conventional housing, mutants develop colitis, indicating that colitis development is dependent on the enteric microbiota

• inflammation is characterized by multifocal aggregates of inflammatory cells in the mucosa and extends transmurally to the submucosa

• inflammation in the lamina propria is occasionally organized into de novo lymphoid follicles and multinucleated giant cells are detected

• CD3+, B220+, and F4/80+ cells are increased in inflamed colonic lamina propria, with the most increase in F4/80+ cells

abnormal leukocyte morphology ( J:209365 )

• decrease in lymphoid tissue inducer cells; RORgammat+ and RORgammat-CD3-NKp46+ colonic lamina propria innate lymphoid cell populations are decreased

• CD4+ and CD4- populations are decreased among CD3-NKp46-RORgammat+ lymphoid tissue inducer cells

decreased NK cell number ( J:209365 )

• decrease in colonic NK cells; the lamina propria CD3-NK1.1+ NK cell population is decreased

• however, the CD3+NK1.1+ NKT cell numbers are normal

increased T-helper 17 cell number ( J:209365 )

• IFN-gamma and IL-17A-producing CD4+ T cells are increased in mutants

abnormal plasma cell morphology ( J:209365 )

• B220+ plasma cells are localized inside and outside of secondary lymphoid follicles instead of within lymphoid structures as in wild-type mice

increased macrophage cytokine production ( J:209365 )

• colonic macrophages are the main source of inflammatory cytokines

abnormal circulating cytokine level ( J:209365 )

increased circulating interferon-gamma level ( J:209365 )

increased circulating interleukin-10 level ( J:209365 )

increased circulating interleukin-12b level ( J:209365 )

increased circulating interleukin-17 level ( J:209365 )

• serum IL-17A is increased

increased circulating tumor necrosis factor level ( J:209365 )

• serum TNF-alpha is increased

abnormal cytokine secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of proinflammatory cytokines

increased interferon-gamma secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of INF-gamma

increased interleukin-10 secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of Il-10

increased interleukin-12b secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of IL-12b (IL-12p40)

increased interleukin-17 secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of IL-17A

increased tumor necrosis factor secretion ( J:209365 )

• colonic tissue explants secrete elevated levels of TNF-alpha

digestive/alimentary system

intestinal ulcer ( J:209365 )

• areas of ulceration

abnormal colon morphology ( J:209365 )

• colons from 12 week old mutants are thickened and foreshortened, with lack of formed fetal pellets

• elongation of colonic crypts

abnormal colon goblet cell morphology ( J:209365 )

• decrease in goblet cells in the colon

rectal prolapse ( J:209365 )

• about 12%, 20 and 50% of mutants develop rectal prolapse by 16, 20 and 36 weeks of age, respectively

colitis ( J:209365 )

• mice develop spontaneous chronic colitis that is Th1/Th7 mediated; colitis is variable and shows incomplete penetrance

• mice derived in a germ-free environment do not exhibit colitis at 6 months of age, however, upon transition from germ-free to conventional housing, mutants develop colitis, indicating that colitis development is dependent on the enteric microbiota

• inflammation is characterized by multifocal aggregates of inflammatory cells in the mucosa and extends transmurally to the submucosa

• inflammation in the lamina propria is occasionally organized into de novo lymphoid follicles and multinucleated giant cells are detected

• CD3+, B220+, and F4/80+ cells are increased in inflamed colonic lamina propria, with the most increase in F4/80+ cells

hematopoietic system

abnormal leukocyte morphology ( J:209365 )

• decrease in lymphoid tissue inducer cells; RORgammat+ and RORgammat-CD3-NKp46+ colonic lamina propria innate lymphoid cell populations are decreased

• CD4+ and CD4- populations are decreased among CD3-NKp46-RORgammat+ lymphoid tissue inducer cells

decreased NK cell number ( J:209365 )

• decrease in colonic NK cells; the lamina propria CD3-NK1.1+ NK cell population is decreased

• however, the CD3+NK1.1+ NKT cell numbers are normal

increased T-helper 17 cell number ( J:209365 )

• IFN-gamma and IL-17A-producing CD4+ T cells are increased in mutants

abnormal plasma cell morphology ( J:209365 )

• B220+ plasma cells are localized inside and outside of secondary lymphoid follicles instead of within lymphoid structures as in wild-type mice

increased macrophage cytokine production ( J:209365 )

• colonic macrophages are the main source of inflammatory cytokines

homeostasis/metabolism

abnormal circulating cytokine level ( J:209365 )

increased circulating interferon-gamma level ( J:209365 )

increased circulating interleukin-10 level ( J:209365 )

increased circulating interleukin-12b level ( J:209365 )

increased circulating interleukin-17 level ( J:209365 )

• serum IL-17A is increased

increased circulating tumor necrosis factor level ( J:209365 )

• serum TNF-alpha is increased

endocrine/exocrine glands

abnormal colon goblet cell morphology ( J:209365 )

• decrease in goblet cells in the colon

cellular

abnormal colon goblet cell morphology ( J:209365 )

• decrease in goblet cells in the colon

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:209365