Phenotypes associated with this allele

• Allele Symbol: Tnf^tm1Jods
• Allele Name: targeted mutation 1, Johnathon D Sedgwick
• Allele ID: MGI:1860953
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnf^tm1Jods/Tnf^tm1Jods	C57BL/6-Lta^tm1Jods	MGI:3768357
hm2	Tnf^tm1Jods/Tnf^tm1Jods	C57BL/6-Tnf^tm1Jods	MGI:3700958
hm3	Tnf^tm1Jods/Tnf^tm1Jods	involves: C57BL/6	MGI:3582921

Genotype
MGI:3768357

hm1

• Allelic Composition: Tnf^tm1Jods/Tnf^tm1Jods
• Genetic Background: C57BL/6-Lta^tm1Jods

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

immune system

abnormal spleen B cell follicle morphology ( J:78229 )

• B cell follicles are replaced by a rim-like structure and the T and B cell areas are less distinct

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:47428 )

• onset of experimental autoimmune encephalomyelitis (EAE) is delayed by 6 days and the overall duration is reduced compared to in wild-type mice

• treatment of mice with TNFR-IgG does not alter disease course as in wild-type mice

• however, the progress of EAE parallels that in wild-type mice

hematopoietic system

abnormal spleen B cell follicle morphology ( J:78229 )

• B cell follicles are replaced by a rim-like structure and the T and B cell areas are less distinct

Genotype
MGI:3700958

hm2

• Allelic Composition: Tnf^tm1Jods/Tnf^tm1Jods
• Genetic Background: C57BL/6-Tnf^tm1Jods

immune system

abnormal cytokine level ( J:118417 )

• cytokine expression levels are elevated 2-4 days before onset of clinical signs of disease in wild-type, but levels are elevated only at onset of disease in mutants

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:118417 )

• immunization with pertussis toxin results in clinical EAE appearing at day 12 and peaking at ~day 18, while in mutants, clinical manifestation of disease is delayed ~5 days, peaking at ~23 days; duration of disease is reduced in mutants compared to wild type

homeostasis/metabolism

abnormal cytokine level ( J:118417 )

• cytokine expression levels are elevated 2-4 days before onset of clinical signs of disease in wild-type, but levels are elevated only at onset of disease in mutants

Genotype
MGI:3582921

hm3

• Allelic Composition: Tnf^tm1Jods/Tnf^tm1Jods
• Genetic Background: involves: C57BL/6

immune system

increased leukocyte cell number ( J:43602 )

abnormal spleen white pulp morphology ( J:43602 , J:98591 )

• B and T cell zones not well demarcated (J:43602)

• loss of B and T cell area segregation (J:98591)

abnormal metallophilic macrophage morphology ( J:98591 )

• the MOMA-1⁺ marginal zone metallophilic macrophages are absent

abnormal spleen primary B follicle morphology ( J:43602 , J:98591 )

• absence of primary B cell follicles (J:43602)

• B cells form a continuous ring around PALS (J:43602)

• absent primary B cell follicles, with B cells forming a ring-like structure around the T cell area (J:98591)

absent spleen germinal center ( J:98591 )

• no formation of PNA⁺ germinal centers upon immunization

abnormal spleen marginal sinus morphology ( J:43602 )

• no marginal sinus

decreased follicular dendritic cell number ( J:43602 )

• reduced number of follicular dendritic cells in B cell zones of the spleen

abnormal Peyer's patch morphology ( J:43602 , J:98591 )

• loss of defined B and T cell structures, with intermixing of cell types (J:43602)

• reduced number of B cells (J:43602)

• exhibit a flattened appearance and T and B cells intermix freely (J:98591)

abnormal Peyer's patch follicle morphology ( J:43602 )

• single, enlarged follicle

decreased Peyer's patch number ( J:43602 )

small Peyer's patches ( J:43602 )

abnormal lymph node primary follicle morphology ( J:98591 )

• loss of primary B cell follicles

abnormal immune system physiology ( J:98591 )

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:44545 , J:98591 )

• delay in the onset of clinical signs in an experimental autoimmune encephalomyelitis (EAE) model, however, disease progressed with similar severity and incidence as in wild-type once it was established (J:98591)

• development of EAE under suboptimal immunization conditions reduced the incidence of disease below 40%, with mild clinical signs that resolved quickly unlike in wild-type (J:98591)

decreased susceptibility to endotoxin shock ( J:98591 )

• resistant to endotoxic shock induced by both high and low doses of LPS

increased susceptibility to bacterial infection ( J:98170 , J:115034 )

• homozygous null mice were unable to control M. tuberculosis growth, showed massive inflammation with extensive necrosis in the lung, developed pneumonia and had a mean survival time of 33 days (J:98170)

• S. aureus-infected mice exhibit greater weight loss and decreased bacterial clearance compared with similarly treated wild-type mice (J:115034)

hematopoietic system

increased leukocyte cell number ( J:43602 )

abnormal spleen white pulp morphology ( J:43602 , J:98591 )

• B and T cell zones not well demarcated (J:43602)

• loss of B and T cell area segregation (J:98591)

abnormal metallophilic macrophage morphology ( J:98591 )

• the MOMA-1⁺ marginal zone metallophilic macrophages are absent

abnormal spleen primary B follicle morphology ( J:43602 , J:98591 )

• absence of primary B cell follicles (J:43602)

• B cells form a continuous ring around PALS (J:43602)

• absent primary B cell follicles, with B cells forming a ring-like structure around the T cell area (J:98591)

absent spleen germinal center ( J:98591 )

• no formation of PNA⁺ germinal centers upon immunization

abnormal spleen marginal sinus morphology ( J:43602 )

• no marginal sinus