Phenotypes Associated with This Genotype

Genotype
MGI:3622061

• Allelic Composition: Tnf^tm2Gkl/Tnf⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

immune system

intestinal inflammation ( J:136667 )

• elevated chronic and acute inflammatory indices

small intestinal inflammation ( J:54056 , J:92307 , J:204922 )

• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum (J:54056)

• becomes severe by 8 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall (J:54056)

• by 4-7 months of age complete loss of villous structure and rudimental granulomata are seen (J:54056)

• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei (J:92307)

• mutants on a high-fat diet develop accelerated onset of intestinal inflammation compared to wild-type mice (J:204922)

ileum inflammation ( J:204922 )

increased dendritic cell number ( J:204922 )

• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice

abnormal T cell subpopulation ratio ( J:136667 )

• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum

abnormal CD8-positive, alpha beta T cell morphology ( J:136667 )

• at 4 weeks of age, fewer CD8alpha alpha intraepithelial lymphocytes are present in the ileum

• however, no significant difference is seen in the number of CD8alpha beta intraepithelial lymphocytes

abnormal alpha-beta intraepithelial T cell morphology ( J:136667 )

• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers

abnormal T cell physiology ( J:136667 )

• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets

abnormal CD4-positive, alpha-beta T cell physiology ( J:136667 )

• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum

abnormal T-helper 17 cell physiology ( J:204922 )

• mutants show increased Th17-biased lymphocyte infiltration into the lamina propria of the ileum on a high-fat diet compared to wild-type mice

abnormal circulating chemokine level ( J:204922 )

• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice

increased circulating tumor necrosis factor level ( J:54056 , J:204922 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice (J:54056)

• TNF plasma levels are increased at 12 weeks of age in mutants compared to wild-type mice, however high-fat diet does not result in a further increase (J:204922)

decreased inflammatory response ( J:204922 )

• expression analysis indicates that mutants do not show adipose tissue inflammation when fed a high-fat diet as seen in wild-type mice

autoimmune arthritis ( J:92307 , J:136667 )

• Background Sensitivity: at 9 months arthritis is severe enough to reduce mobility unlike in mice on a mixed background including SPRET/Ei (J:92307)

• at 9 months joints show extensive lymphocytic infiltration, thickening of the synovial lining, pannus formation, and abnormal ingrowth of the synovial lining (J:92307)

rheumatoid arthritis ( J:54056 )

digestive/alimentary system

steatorrhea ( J:204922 )

• mutants show elevated fecal energy content when fed a high-fat diet, suggesting steatorrhea, which is not seen in wild-type mice

abnormal intestine physiology ( J:204922 )

• mutants show increased intestinal permeability when fed a high-fat diet

intestinal inflammation ( J:136667 )

• elevated chronic and acute inflammatory indices

small intestinal inflammation ( J:54056 , J:92307 , J:204922 )

• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum (J:54056)

• becomes severe by 8 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall (J:54056)

• by 4-7 months of age complete loss of villous structure and rudimental granulomata are seen (J:54056)

• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei (J:92307)

• mutants on a high-fat diet develop accelerated onset of intestinal inflammation compared to wild-type mice (J:204922)

ileum inflammation ( J:204922 )

skeleton

autoimmune arthritis ( J:92307 , J:136667 )

• Background Sensitivity: at 9 months arthritis is severe enough to reduce mobility unlike in mice on a mixed background including SPRET/Ei (J:92307)

• at 9 months joints show extensive lymphocytic infiltration, thickening of the synovial lining, pannus formation, and abnormal ingrowth of the synovial lining (J:92307)

rheumatoid arthritis ( J:54056 )

homeostasis/metabolism

steatorrhea ( J:204922 )

• mutants show elevated fecal energy content when fed a high-fat diet, suggesting steatorrhea, which is not seen in wild-type mice

decreased susceptibility to diet-induced obesity ( J:204922 )

• mutants do not develop obesity on a high-fat diet as seen in wild-type mice

• mutants on a high-fat diet do not show increased fat depots or enlarged adipocytes as seen in wild-type mice

abnormal circulating leptin level ( J:204922 )

• mutants on high-fat diet do not exhibit an increase in plasma leptin levels as seen in wild-type mice

abnormal circulating chemokine level ( J:204922 )

• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice

increased circulating tumor necrosis factor level ( J:54056 , J:204922 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice (J:54056)

• TNF plasma levels are increased at 12 weeks of age in mutants compared to wild-type mice, however high-fat diet does not result in a further increase (J:204922)

abnormal glucose homeostasis ( J:204922 )

• glucose homeostasis remains normal in mutants fed a high-fat diet unlike in wild-type mice which show impaired glucose tolerance and elevated fasting blood glucose

hematopoietic system

increased dendritic cell number ( J:204922 )

• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice

abnormal T cell subpopulation ratio ( J:136667 )

• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum

abnormal CD8-positive, alpha beta T cell morphology ( J:136667 )

• at 4 weeks of age, fewer CD8alpha alpha intraepithelial lymphocytes are present in the ileum

• however, no significant difference is seen in the number of CD8alpha beta intraepithelial lymphocytes

abnormal alpha-beta intraepithelial T cell morphology ( J:136667 )

• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers

abnormal T cell physiology ( J:136667 )

• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets

abnormal CD4-positive, alpha-beta T cell physiology ( J:136667 )

• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum

abnormal T-helper 17 cell physiology ( J:204922 )

• mutants show increased Th17-biased lymphocyte infiltration into the lamina propria of the ileum on a high-fat diet compared to wild-type mice

integument

alopecia ( J:92307 )

• at 9 months of age

behavior/neurological

abnormal food intake ( J:204922 )

• mutants exhibit increased energy intake on a high-fat diet

growth/size/body

decreased susceptibility to diet-induced obesity ( J:204922 )

• mutants do not develop obesity on a high-fat diet as seen in wild-type mice

• mutants on a high-fat diet do not show increased fat depots or enlarged adipocytes as seen in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:54056 , J:136667 , J:204922
rheumatoid arthritis		DOID:7148	OMIM:180300	J:54056