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Phenotypes Associated with This Genotype
Genotype
MGI:3622061
Allelic
Composition
Tnftm2Gkl/Tnf+
Genetic
Background
involves: 129S/SvEv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm2Gkl mutation (1 available); any Tnf mutation (35 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• elevated chronic and acute inflammatory indices
• 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)
• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice
• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum
• 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
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers
• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets
• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum
• mutants show increased Th17-biased lymphocyte infiltration into the lamina propria of the ileum on a high-fat diet compared to wild-type mice
• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice
• 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)
• expression analysis indicates that mutants do not show adipose tissue inflammation when fed a high-fat diet as seen in wild-type mice
• 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)

digestive/alimentary system
• mutants show elevated fecal energy content when fed a high-fat diet, suggesting steatorrhea, which is not seen in wild-type mice
• mutants show increased intestinal permeability when fed a high-fat diet
• elevated chronic and acute inflammatory indices
• 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)

skeleton
• 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)

homeostasis/metabolism
• mutants show elevated fecal energy content when fed a high-fat diet, suggesting steatorrhea, which is not seen in wild-type mice
• 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
• mutants on high-fat diet do not exhibit an increase in plasma leptin levels as seen in wild-type mice
• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice
• 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)
• 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
• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice
• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum
• 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
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers
• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets
• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum
• 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
• at 9 months of age

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

growth/size/body
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
04/09/2019
MGI 6.13
The Jackson Laboratory