Phenotypes Associated with This Genotype

Genotype
MGI:3815320

• Allelic Composition: Lyn^tm1Sor/Lyn^tm1Sor
• Genetic Background: involves: 129S4/SvJaeSor

• ♀: 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

immune system

increased B cell proliferation ( J:146161 )

• B cells form mice 7- to 11- weeks of age hyperproliferate in response to anti-IgM stimulation and LPS

spleen hyperplasia ( J:146161 )

• mice develop splenomegaly with age due to myeloid hyperplasia

myeloid hyperplasia ( J:146161 )

increased plasma cell number ( J:200745 )

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

decreased B cell number ( J:200745 )

decreased transitional stage B cell number ( J:146161 )

• reduced numbers of T1 and T2 B cells are found in the spleen

decreased mature B cell number ( J:146161 )

• peripheral B cell numbers are reduced by almost 10-fold

decreased follicular B cell number ( J:146161 )

• reduced by about 10-fold in the spleen

decreased marginal zone B cell number ( J:146161 )

• reduced numbers in the spleen

increased IgA level ( J:146161 )

• mice have elevated levels of IgA in sera

increased IgM level ( J:146161 )

• mice have elevated levels of IgM in sera

abnormal macrophage physiology ( J:80658 )

• fibrillar beta-amyloid stimulated reactive oxygen species production is reduced 70% compared to in wild-type cells

• however, response to zymosan and macrophage recruitment are normal

abnormal microglial cell physiology ( J:80658 )

• fibrillar beta-amyloid stimulated microglial recruitment is reduced 3-fold compared to in wild-type mice

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-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

abnormal chemokine level ( J:80658 )

• fibrillar beta-amyloid stimulated MCP-1 production in macrophages is reduced by 50% compared to in wild-type mice

• however, macrophage production of MCP-1 in response to LPS or reverse beta-amyloid is normal

abnormal dendritic cell physiology ( J:200745 )

• splenic dendritic cells produce more proinflammatory cytokines and more chemokines

• CD11c^hi DCs are hyperresponsive to cytokine stimulation

increased autoantibody level ( J:200745 )

• high levels of autoreactive antibodies in the serum

increased anti-double stranded DNA antibody level ( J:146161 )

• serum levels of anti-dsDNA antibodies increase with age with high levels occurring by 12 months of age

• levels of anti-dsDNA antibodies are below those of age-matched Lyn null homozygotes

liver inflammation ( J:146161 )

• IgG depositions in the liver occur in older mice though no associated pathology is observed

glomerulonephritis ( J:146161 , J:200745 )

• mice develop severe glomerulonephritis around 8 months of age (J:146161)

• disease includes enlarged glomeruli, glomerular, hypercellularity, lobularity and sclerosis, mesangial interposition in peripheral capillary loops, and strong IgG deposition in the glomeruli (J:146161)

• glomerulonephritis without interstitial inflammation is seen by 8-10 months of age (J:200745)

nervous system

abnormal microglial cell physiology ( J:80658 )

• fibrillar beta-amyloid stimulated microglial recruitment is reduced 3-fold compared to in wild-type mice

renal/urinary system

mesangial cell interposition ( J:146161 )

• mesangial interposition in peripheral capillary loops

glomerulonephritis ( J:146161 , J:200745 )

• mice develop severe glomerulonephritis around 8 months of age (J:146161)

• disease includes enlarged glomeruli, glomerular, hypercellularity, lobularity and sclerosis, mesangial interposition in peripheral capillary loops, and strong IgG deposition in the glomeruli (J:146161)

• glomerulonephritis without interstitial inflammation is seen by 8-10 months of age (J:200745)

glomerulosclerosis ( J:146161 )

renal glomerular protein deposits ( J:200745 )

• deposition of C3 in the glomeruli

renal glomerulus hypertrophy ( J:146161 )

• enlarged glomeruli

liver/biliary system

liver inflammation ( J:146161 )

• IgG depositions in the liver occur in older mice though no associated pathology is observed

hematopoietic system

increased B cell proliferation ( J:146161 )

• B cells form mice 7- to 11- weeks of age hyperproliferate in response to anti-IgM stimulation and LPS

spleen hyperplasia ( J:146161 )

• mice develop splenomegaly with age due to myeloid hyperplasia

myeloid hyperplasia ( J:146161 )

increased erythroid progenitor cell number ( J:146561 )

• mice exhibit an accumulation of erythroid progenitor cells in the Kit+CD71^high compartment compared to in wild-type mice

abnormal proerythroblast morphology ( J:146561 )

• the ratio of Kit+ to Kit- proerythroblasts is increased compared to in wild-type mice

increased plasma cell number ( J:200745 )

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

decreased B cell number ( J:200745 )

decreased transitional stage B cell number ( J:146161 )

• reduced numbers of T1 and T2 B cells are found in the spleen

decreased mature B cell number ( J:146161 )

• peripheral B cell numbers are reduced by almost 10-fold

decreased follicular B cell number ( J:146161 )

• reduced by about 10-fold in the spleen

decreased marginal zone B cell number ( J:146161 )

• reduced numbers in the spleen

increased IgA level ( J:146161 )

• mice have elevated levels of IgA in sera

increased IgM level ( J:146161 )

• mice have elevated levels of IgM in sera

abnormal macrophage physiology ( J:80658 )

• fibrillar beta-amyloid stimulated reactive oxygen species production is reduced 70% compared to in wild-type cells

• however, response to zymosan and macrophage recruitment are normal

abnormal microglial cell physiology ( J:80658 )

• fibrillar beta-amyloid stimulated microglial recruitment is reduced 3-fold compared to in wild-type mice

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-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

abnormal chemokine level ( J:80658 )

• fibrillar beta-amyloid stimulated MCP-1 production in macrophages is reduced by 50% compared to in wild-type mice

• however, macrophage production of MCP-1 in response to LPS or reverse beta-amyloid is normal

cellular

mesangial cell interposition ( J:146161 )

• mesangial interposition in peripheral capillary loops

increased B cell proliferation ( J:146161 )

• B cells form mice 7- to 11- weeks of age hyperproliferate in response to anti-IgM stimulation and LPS

abnormal microglial cell physiology ( J:80658 )

• fibrillar beta-amyloid stimulated microglial recruitment is reduced 3-fold compared to in wild-type mice

growth/size/body

spleen hyperplasia ( J:146161 )

• mice develop splenomegaly with age due to myeloid hyperplasia