Phenotypes associated with this allele

• Allele Symbol: Tnfsf10^tm1Mjs
• Allele Name: targeted mutation 1, Mark J Smyth
• Allele ID: MGI:2179709
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfsf10^tm1Mjs/Tnfsf10^tm1Mjs	B6.129-Tnfsf10^tm1Mjs	MGI:4358703
hm2	Tnfsf10^tm1Mjs/Tnfsf10^tm1Mjs	C.129-Tnfsf10^tm1Mjs	MGI:4358597

Genotype
MGI:4358703

hm1

• Allelic Composition: Tnfsf10^tm1Mjs/Tnfsf10^tm1Mjs
• Genetic Background: B6.129-Tnfsf10^tm1Mjs

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

immune system

immune system phenotype ( J:84838 )

N • defective negative selection of T cells observed in one study is not observed in this study

thymus hyperplasia ( J:82145 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age

abnormal negative T cell selection ( J:82145 )

• anti-CD3 fails to induce apoptosis of CD4⁺CD8⁺ thymocytes in vivo, or in fetal thymic organ culture

increased IgG1 level ( J:82145 )

• there are higher levels of antigen-specific IgG1 in mice immunized with collagen compared to controls

increased IgG2a level ( J:82145 )

• there are higher levels of antigen-specific IgG2a in mice immunized with collagen compared to controls

increased interferon-gamma secretion ( J:82145 )

• splenocyte IFN-gamma secretion is enhanced from collagen-immunized mice upon reencounter with antigen compared to controls

increased interleukin-2 secretion ( J:82145 )

• splenocyte IL-2 secretion is enhanced from collagen-immunized mice upon reencounter with antigen compared to controls

increased susceptibility to autoimmune diabetes ( J:82145 )

• streptozotocin induced diabetes has an earlier onset, higher incidence and is more severe than in controls mice

• onset of disease is first detected 20 days after injection compared to over 30 days for controls

• incidence reaches 80% versus 40% of controls

• insulitis and islet destruction is much more severe than in streptozotocin-injected wild-type mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:101672 )

• mice have increased susceptibility to EAE induced by peptide derived from myelin oligodendrocyte glycoprotein (MOG)

• 2 of 6 mice die within 40 days of MOG administration compared to none of the wild-type controls

• mean maximal disease score and cumulative disease scores are significantly higher than controls

increased susceptibility to induced arthritis ( J:82145 )

• mice develop severe arthritis 4 weeks after collagen immunization compared to C57BL/6 controls that do not develop disease

• arthritis is characterized by footpad swelling, pannus formation, cartilage destruction of paw joints

hematopoietic system

hematopoietic system phenotype ( J:84838 )

N • defective negative selection of T cells observed in one study is not observed in this study

thymus hyperplasia ( J:82145 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age

abnormal negative T cell selection ( J:82145 )

• anti-CD3 fails to induce apoptosis of CD4⁺CD8⁺ thymocytes in vivo, or in fetal thymic organ culture

increased IgG1 level ( J:82145 )

• there are higher levels of antigen-specific IgG1 in mice immunized with collagen compared to controls

increased IgG2a level ( J:82145 )

• there are higher levels of antigen-specific IgG2a in mice immunized with collagen compared to controls

skeleton

increased susceptibility to induced arthritis ( J:82145 )

• mice develop severe arthritis 4 weeks after collagen immunization compared to C57BL/6 controls that do not develop disease

• arthritis is characterized by footpad swelling, pannus formation, cartilage destruction of paw joints

endocrine/exocrine glands

thymus hyperplasia ( J:82145 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age

Genotype
MGI:4358597

hm2

• Allelic Composition: Tnfsf10^tm1Mjs/Tnfsf10^tm1Mjs
• Genetic Background: C.129-Tnfsf10^tm1Mjs

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:87620 )

• mice have increased survivor rates 3 and 7 days after Listeria monocytogenes infection compared to controls

immune system

immune system phenotype ( J:84838 )

N • the defective negative selection of T cells observed in one study is not observed in this study

thymus hyperplasia ( J:82145 , J:84838 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age (J:82145)

• mean thymic cellularity is increased about 20% (J:84838)

abnormal negative T cell selection ( J:82145 )

• Background Sensitivity: negative selection mediated by mammary tumor virus-9 antigen is restricted to mice expressing I-E ( eg BALB/c) and does not occur in mice without I-E expression (C57BL/6)

• Background Sensitivity: Mtv(9)-induced negative selection of Vbeta3, Vbeta5, and Vbeta11 T cells is impaired in these mice compared to BALB/c controls

• Background Sensitivity: these T cells are functional as determined by beta-chain specific antibodies that induce cytokine secretion

impaired natural killer cell mediated cytotoxicity ( J:73948 )

• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells

• there is less NK-mediated tumor lysis when Renca tumor cells are inoculated into mutant mice

• this results in increased metastasis in liver especially at lower tumor cell doses

• similar results are seen with 4T1 tumor cells when they are injected into the mammary gland

liver inflammation ( J:87620 )

• mice are resistant to hepatitis induced by ConA administration

• mice fail to develop liver lesions though some inflammatory infiltrates are observed

• the number of apoptotic cells in the liver 24 hours after ConA injection is significantly reduced compared to controls

• hepatitis associated with Listeria infection is also much less severe compared to controls

decreased susceptibility to bacterial infection ( J:87620 )

• mice are resistant to Listeria monocytogenes infection

• CFU are 100-fold lower in the liver compared to controls 3 days after infection

• hepatitis associated with Listeria infection is much less severe compared to controls

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:87620 )

• mice have increased survivor rates 3 and 7 days after Listeria monocytogenes infection compared to controls

neoplasm

increased incidence of induced tumors ( J:73948 )

• mice are more prone to developing metastasis from inoculation of low numbers of 4T1 or Renca tumor target cells

increased incidence of tumors by chemical induction ( J:73948 )

• injection of the low dose (100 microgram) chemical carcinogen MCA leads to three times more fibrosarcomas that occur with an earlier incidence

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:73948 )

• injection of the low dose (100 microgram) chemical carcinogen MCA leads to three times more fibrosarcomas that occur with an earlier incidence

hematopoietic system

hematopoietic system phenotype ( J:84838 )

N • the defective negative selection of T cells observed in one study is not observed in this study

thymus hyperplasia ( J:82145 , J:84838 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age (J:82145)

• mean thymic cellularity is increased about 20% (J:84838)

abnormal negative T cell selection ( J:82145 )

• Background Sensitivity: negative selection mediated by mammary tumor virus-9 antigen is restricted to mice expressing I-E ( eg BALB/c) and does not occur in mice without I-E expression (C57BL/6)

• Background Sensitivity: Mtv(9)-induced negative selection of Vbeta3, Vbeta5, and Vbeta11 T cells is impaired in these mice compared to BALB/c controls

• Background Sensitivity: these T cells are functional as determined by beta-chain specific antibodies that induce cytokine secretion

impaired natural killer cell mediated cytotoxicity ( J:73948 )

• activated splenic and liver NK cells are less efficient in their killing of 4T1 or Renca tumor target cells

• there is less NK-mediated tumor lysis when Renca tumor cells are inoculated into mutant mice

• this results in increased metastasis in liver especially at lower tumor cell doses

• similar results are seen with 4T1 tumor cells when they are injected into the mammary gland

liver/biliary system

liver inflammation ( J:87620 )

• mice are resistant to hepatitis induced by ConA administration

• mice fail to develop liver lesions though some inflammatory infiltrates are observed

• the number of apoptotic cells in the liver 24 hours after ConA injection is significantly reduced compared to controls

• hepatitis associated with Listeria infection is also much less severe compared to controls

endocrine/exocrine glands

thymus hyperplasia ( J:82145 , J:84838 )

• mean thymic cellularity is increased about 10% at 6-7 weeks of age (J:82145)

• mean thymic cellularity is increased about 20% (J:84838)