Phenotypes Associated with This Genotype

Genotype
MGI:5545813

• Allelic Composition: Lyn^tm1.1Calo/Lyn^tm1.1Calo; Tg(Itgax-cre)1-1Reiz/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

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

Lupus-like autoimmune disease in Lyn^tm1Sor/Lyn^tm1Sor and Lyn^tm1.1Calo/Lyn^tm1.1Calo Top2a^{Gt(PST14568)Mfgc}/0 mice

mortality/aging

premature death ( J:200745 )

• average survival time of 8 months

immune system

enlarged spleen ( J:200745 )

• severe splenomegaly starting at 6 months of age

• spleens are 16- and 7.9-fold larger than those in controls and mice homozygous for Lyn^tm1Sor, respectively

myeloid hyperplasia ( J:200745 )

• dramatic expansion of myeloid compartment in the spleen and lymph nodes

• myeloid proliferations occurs earlier than in mice homozygous for Lyn^tm1Sor

increased dendritic cell number ( J:200745 )

• increase in the numbers of CD11c^hi MHCII+ conventional DCs and CD11c^lo B220+ Ly6C+ plasmacytoid DCs in the spleen and lymph nodes over time

increased leukocyte cell number ( J:200745 )

• increased numbers of monocytes/macrophages in the spleen and lymph nodes at 4 months of age

increased granulocyte number ( J:200745 )

• in the spleen and lymph nodes at 4 months of age

increased plasma cell number ( J:200745 )

• increase in the number of CD19^lo/- CD138^hi plasma cells in the spleen

increased T cell number ( J:200745 )

• high numbers of CD44^hi CD62L^lo/- effector T cells and CD69+ T cells

increased activated T cell number ( J:200745 )

• in secondary lymphoid organs

increased monocyte cell number ( J:200745 )

• in the spleen and lymph nodes at 4 months of age

abnormal leukocyte physiology ( J:200745 )

• myeloid cells are hyperresponsive to LPS

abnormal T cell activation ( J:200745 )

• in secondary lymphoid organs

abnormal circulating cytokine level ( J:200745 )

• increased levels of granulocyte and granulocyte macrophage colony stimulating factors at 6 months of age

• high levels of circulating B-cell activating factor

abnormal circulating chemokine level ( J:200745 )

• increased levels of a number of chemokines at 6 months of age

increased circulating interferon-gamma level ( J:200745 )

• at 6 months of age

increased circulating interleukin-1 beta level ( J:200745 )

• at 6 months of age

increased circulating interleukin-12 level ( J:200745 )

• at 6 months of age

increased circulating interleukin-17 level ( J:200745 )

• at 6 months of age

increased circulating interleukin-6 level ( J:200745 )

• at 6 months of age

increased circulating tumor necrosis factor level ( J:200745 )

• at 6 months of age

enlarged lymph nodes ( J:200745 )

• increase in lymph node size and cellularity as early as 4 months of age, mainly due to increased numbers of T cells myeloid cells and dendritic cells

lymph node hyperplasia ( J:200745 )

abnormal dendritic cell physiology ( J:200745 )

• following exposure to Brefeldin A and LPS, splenic dendritic cells produce high levels of inflammatory cytokines

• CD11c^hi DCs are hyperresponsive to cytokine stimulation

increased autoantibody level ( J:200745 )

• high levels of autoreactive antibodies in the serum

increased inflammatory response ( J:200745 )

• by 8 months of age, 60-70% of mice display severe leukocyte infiltration in the lungs, liver, and skin

liver inflammation ( J:200745 )

glomerulonephritis ( J:200745 )

• enlarged glomeruli and increased leukocyte infiltration indicative of glomerulonephritis at 6 months of age

• abundant leukocyte infiltration in the interstitial tissue at 6 months of age

lung inflammation ( J:200745 )

skin inflammation ( J:200745 )

integument

skin inflammation ( J:200745 )

skin lesions ( J:200745 )

• develop macroscopic skin lesions starting around 6 months of age

renal/urinary system

glomerulonephritis ( J:200745 )

• enlarged glomeruli and increased leukocyte infiltration indicative of glomerulonephritis at 6 months of age

• abundant leukocyte infiltration in the interstitial tissue at 6 months of age

renal glomerular immunoglobulin deposits ( J:200745 )

• deposition of C3 in the glomeruli

homeostasis/metabolism

abnormal circulating cytokine level ( J:200745 )

• increased levels of granulocyte and granulocyte macrophage colony stimulating factors at 6 months of age

• high levels of circulating B-cell activating factor

abnormal circulating chemokine level ( J:200745 )

• increased levels of a number of chemokines at 6 months of age

increased circulating interferon-gamma level ( J:200745 )

• at 6 months of age

increased circulating interleukin-1 beta level ( J:200745 )

• at 6 months of age

increased circulating interleukin-12 level ( J:200745 )

• at 6 months of age

increased circulating interleukin-17 level ( J:200745 )

• at 6 months of age

increased circulating interleukin-6 level ( J:200745 )

• at 6 months of age

increased circulating tumor necrosis factor level ( J:200745 )

• at 6 months of age

liver/biliary system

liver inflammation ( J:200745 )

respiratory system

lung inflammation ( J:200745 )

hematopoietic system

enlarged spleen ( J:200745 )

• severe splenomegaly starting at 6 months of age

• spleens are 16- and 7.9-fold larger than those in controls and mice homozygous for Lyn^tm1Sor, respectively

myeloid hyperplasia ( J:200745 )

• dramatic expansion of myeloid compartment in the spleen and lymph nodes

• myeloid proliferations occurs earlier than in mice homozygous for Lyn^tm1Sor

increased dendritic cell number ( J:200745 )

• increase in the numbers of CD11c^hi MHCII+ conventional DCs and CD11c^lo B220+ Ly6C+ plasmacytoid DCs in the spleen and lymph nodes over time

increased leukocyte cell number ( J:200745 )

• increased numbers of monocytes/macrophages in the spleen and lymph nodes at 4 months of age

increased granulocyte number ( J:200745 )

• in the spleen and lymph nodes at 4 months of age

increased plasma cell number ( J:200745 )

• increase in the number of CD19^lo/- CD138^hi plasma cells in the spleen

increased T cell number ( J:200745 )

• high numbers of CD44^hi CD62L^lo/- effector T cells and CD69+ T cells

increased activated T cell number ( J:200745 )

• in secondary lymphoid organs

increased monocyte cell number ( J:200745 )

• in the spleen and lymph nodes at 4 months of age

abnormal leukocyte physiology ( J:200745 )

• myeloid cells are hyperresponsive to LPS

abnormal T cell activation ( J:200745 )

• in secondary lymphoid organs

growth/size/body

enlarged spleen ( J:200745 )

• severe splenomegaly starting at 6 months of age

• spleens are 16- and 7.9-fold larger than those in controls and mice homozygous for Lyn^tm1Sor, respectively