Phenotypes associated with this allele

• Allele Symbol: Tnf^tm1.1Sned
• Allele Name: targeted mutation 1.1, Sergei A Nedospasov
• Allele ID: MGI:3527143
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tnf^tm1.1Sned/Tnf^tm1.1Sned Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129 * 129P2/OlaHsd * C57BL/6	MGI:3527247
cn2	Tnf^tm1.1Sned/Tnf^tm1.1Sned Cd19^tm1(cre)Cgn/Cd19^+	involves: 129 * 129P2/OlaHsd * C57BL/6	MGI:3527259
cn3	Tnf^tm1.1Sned/Tnf^tm1.1Sned Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2	MGI:3527254

Genotype
MGI:3527247

cn1

• Allelic Composition: Tnf^tm1.1Sned/Tnf^tm1.1Sned; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:95684 )

• died within 4 days after Listeria monocytogenes infection whereas controls survived

immune system

decreased circulating tumor necrosis factor level ( J:95684 )

• serum TNF levels were dramatically reduced in mutants injected with LPS, with TNF production decreased by 100-fold in macrophages

abnormal chemokine secretion ( J:95684 )

• induction of MCP-1 was reduced in spleens of mutants infected with Listeria monocytogenes

decreased susceptibility to autoimmune disorder ( J:95684 )

• increased resistance to liver injury after ConA-induced autoimmune hepatitis

decreased susceptibility to endotoxin shock ( J:95684 )

• fully resistant to lipopolysaccharide (LPS)/D-Gal induced septic shock

• protected from toxic shock induced by enterotoxin B, a superantigen from S. aureus

increased susceptibility to bacterial infection ( J:95684 )

• loss of resistance against Listeria monocytogenes, developing uncontrolled infection, leading to death within 4 days and a 3-4 log increase in bacterial load in the liver and spleen

liver/biliary system

hepatic necrosis ( J:95684 )

• mutants infected with Listeria monocytogenes developed large, confluent inflammatory necrotic areas with many Mac-1 and Gr1-positive cells

• no liver necrosis, only infiltrating cells, were detected in mutants with ConA induced autoimmune hepatitis

homeostasis/metabolism

decreased circulating tumor necrosis factor level ( J:95684 )

• serum TNF levels were dramatically reduced in mutants injected with LPS, with TNF production decreased by 100-fold in macrophages

cellular

hepatic necrosis ( J:95684 )

• mutants infected with Listeria monocytogenes developed large, confluent inflammatory necrotic areas with many Mac-1 and Gr1-positive cells

• no liver necrosis, only infiltrating cells, were detected in mutants with ConA induced autoimmune hepatitis

Genotype
MGI:3527259

cn2

• Allelic Composition: Tnf^tm1.1Sned/Tnf^tm1.1Sned; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:95684 )

N • susceptibility to LPS, S. aureus, and Listeria monocytoegenes infection and liver injury was not different from wild-type and no differences in serum TNF levels were detected, indicating that B cell derived Tnf does not play a role in toxicity, host defense, or autoimmunity

Genotype
MGI:3527254

cn3

• Allelic Composition: Tnf^tm1.1Sned/Tnf^tm1.1Sned; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:95684 )

• increased mortality (40%) on days 5-8 post Listeria monocytogenes infection compared to controls

immune system

decreased circulating tumor necrosis factor level ( J:95684 )

• no difference in serum TNF levels after LPS injection compared to wild-type, however serum TNF levels were decreased after liver injury

decreased susceptibility to autoimmune disorder ( J:95684 )

• increased resistance to liver injury after ConA-induced autoimmune hepatitis

decreased susceptibility to endotoxin shock ( J:95684 )

• protected from S. aureus enterotoxin B induced toxic shock but no difference from wild-type after LPS challenge

increased susceptibility to bacterial infection ( J:95684 )

• increased sensitivity to Listeria monocytogenes at high doses of infection, with elevated bacterial load on day 4 or 6 and increased mortality, although survivors were able to clear the bacteria by day 14

homeostasis/metabolism

decreased circulating tumor necrosis factor level ( J:95684 )

• no difference in serum TNF levels after LPS injection compared to wild-type, however serum TNF levels were decreased after liver injury