Phenotypes Associated with This Genotype

Genotype
MGI:5296231

• Allelic Composition: Tnip1^tm1.1Pcoh/Tnip1^tm1.1Pcoh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:176826 )

• by 6 months of age, exacerbated in female mice during pregnancy

immune system

immune system phenotype ( J:176826 )

N • mice exhibit normal stimulated T cell proliferation and cytokine production

increased B cell proliferation ( J:176826 )

• when stimulated by TLR4 agonist LPS, the TLR2/6 agonist lipoteichoic acid (LTA), the TLR7 agonist R848, or anti-IgM and anti-CD40 antibodies

• however, proliferation in response to the TLR9 ligand ODN1826 is normal

increased immunoglobulin level ( J:176826 )

increased IgA level ( J:176826 )

increased IgE level ( J:176826 )

increased IgG level ( J:176826 )

increased IgG1 level ( J:176826 )

increased IgG2a level ( J:176826 )

increased IgG2b level ( J:176826 )

increased IgG3 level ( J:176826 )

increased IgM level ( J:176826 )

abnormal immune system morphology ( J:176826 )

• severe autoimmunity is exacerbated in female mice during pregnancy

enlarged spleen ( J:176826 )

• at 2 to 3 months of age

increased spleen weight ( J:176826 )

• 4 to 5 times at 4 months of age

increased granulocyte number ( J:176826 )

• in the spleen and lymph node

increased B cell number ( J:176826 )

• in the spleen and lymph node

increased germinal center B cell number ( J:176826 )

• in the spleen and lymph node

increased plasma cell number ( J:176826 )

• in the Peyer's Patch, peribronchial lymphoid tissue, hepatic portal tracts

increased monocyte cell number ( J:176826 )

• 4 to 5 times in the blood

abnormal plasma cell morphology ( J:176826 )

• in the Peyer's Patch, peribronchial lymphoid tissue, hepatic portal tracts

abnormal effector T cell morphology ( J:176826 )

• mice exhibit an increase in the proportion of activated effector T cells and a decrease in the proportion of naive cells in the spleen and lymph nodes compared with wild-type mice

• however, the proportion of CD4+ and CD8+ T cells is normal in the spleen

increased T follicular helper cell number ( J:176826 )

• mice exhibit an increase in the proportion of activated effector T cells and a decrease in the proportion of naive cells in the spleen and lymph nodes compared with wild-type mice

• however, the proportion of CD4+ and CD8+ T cells is normal in the spleen

increased spleen red pulp amount ( J:176826 )

• without loss of spleen architecture

abnormal spleen germinal center morphology ( J:176826 )

• splenic germinal center formation is increased compared to in wild-type mice

increased spleen white pulp amount ( J:176826 )

• without loss of spleen architecture

abnormal Peyer's patch morphology ( J:176826 )

• Peyer's patches exhibit plasma cells and neutrophils

enlarged lymph nodes ( J:176826 )

abnormal complement pathway ( J:176826 )

• mice exhibit immune complex deposition (C3, C1q, and IgG) in the kidney unlike wild-type mice

increased interleukin-12b secretion ( J:176826 )

• from B cells stimulated with LPS alone or with anti-CD40 antibodies

increased interleukin-6 secretion ( J:176826 )

• from B cells stimulated with LPS alone or with anti-CD40 antibodies or TLR stimulated bone marrow-derived dendritic cells

increased tumor necrosis factor secretion ( J:176826 )

• from TLR stimulated bone marrow-derived dendritic cells

increased anti-nuclear antigen antibody level ( J:176826 )

increased anti-double stranded DNA antibody level ( J:176826 )

• after 16 and 20 weeks

glomerulonephritis ( J:176826 )

• at 20 to 24 weeks, mice develop severe renal disease (severe generalized global membranoproliferative glomerulonephritis with infiltration of neutrophils and plasma cells and thickening of glomerular capillary loops and Bowman's capsule basement membrane regions)

cardiovascular system

abnormal blood vessel morphology ( J:176826 )

• mice develop vascular lesions in arterioles of the spleen and heart and occasionally Peyer's Patch arterioles and peripancreatic arteries

vascular inflammation ( J:176826 )

• with severe inflammatory cell infiltrate

cellular

increased fibroblast apoptosis ( J:176826 )

• in TNF-treated mouse embryonic fibroblasts

increased B cell proliferation ( J:176826 )

• when stimulated by TLR4 agonist LPS, the TLR2/6 agonist lipoteichoic acid (LTA), the TLR7 agonist R848, or anti-IgM and anti-CD40 antibodies

• however, proliferation in response to the TLR9 ligand ODN1826 is normal

digestive/alimentary system

abnormal intestine morphology ( J:176826 )

• intestinal nodules

endocrine/exocrine glands

bile duct hyperplasia ( J:176826 )

liver/biliary system

bile duct hyperplasia ( J:176826 )

liver fibrosis ( J:176826 )

• mice exhibit hepatic portal tract lesions with increased numbers of hematopoietic cells, lymphocytes, plasma cells, macrophages, neutrophils, bridging fibrosis and biliary hyperplasia

renal/urinary system

glomerulonephritis ( J:176826 )

• at 20 to 24 weeks, mice develop severe renal disease (severe generalized global membranoproliferative glomerulonephritis with infiltration of neutrophils and plasma cells and thickening of glomerular capillary loops and Bowman's capsule basement membrane regions)

hematopoietic system

increased B cell proliferation ( J:176826 )

• when stimulated by TLR4 agonist LPS, the TLR2/6 agonist lipoteichoic acid (LTA), the TLR7 agonist R848, or anti-IgM and anti-CD40 antibodies

• however, proliferation in response to the TLR9 ligand ODN1826 is normal

enlarged spleen ( J:176826 )

• at 2 to 3 months of age

increased spleen weight ( J:176826 )

• 4 to 5 times at 4 months of age

increased granulocyte number ( J:176826 )

• in the spleen and lymph node

increased B cell number ( J:176826 )

• in the spleen and lymph node

increased germinal center B cell number ( J:176826 )

• in the spleen and lymph node

increased plasma cell number ( J:176826 )

• in the Peyer's Patch, peribronchial lymphoid tissue, hepatic portal tracts

increased monocyte cell number ( J:176826 )

• 4 to 5 times in the blood

abnormal plasma cell morphology ( J:176826 )

• in the Peyer's Patch, peribronchial lymphoid tissue, hepatic portal tracts

abnormal effector T cell morphology ( J:176826 )

• mice exhibit an increase in the proportion of activated effector T cells and a decrease in the proportion of naive cells in the spleen and lymph nodes compared with wild-type mice

• however, the proportion of CD4+ and CD8+ T cells is normal in the spleen

increased T follicular helper cell number ( J:176826 )

• mice exhibit an increase in the proportion of activated effector T cells and a decrease in the proportion of naive cells in the spleen and lymph nodes compared with wild-type mice

• however, the proportion of CD4+ and CD8+ T cells is normal in the spleen

increased spleen red pulp amount ( J:176826 )

• without loss of spleen architecture

abnormal spleen germinal center morphology ( J:176826 )

• splenic germinal center formation is increased compared to in wild-type mice

increased spleen white pulp amount ( J:176826 )

• without loss of spleen architecture

increased immunoglobulin level ( J:176826 )

increased IgA level ( J:176826 )

increased IgE level ( J:176826 )

increased IgG level ( J:176826 )

increased IgG1 level ( J:176826 )

increased IgG2a level ( J:176826 )

increased IgG2b level ( J:176826 )

increased IgG3 level ( J:176826 )

increased IgM level ( J:176826 )

growth/size/body

enlarged spleen ( J:176826 )

• at 2 to 3 months of age

increased spleen weight ( J:176826 )

• 4 to 5 times at 4 months of age