Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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behavior/neurological
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• one week following surgery to produce cortical controlled impact (CCI) brain injury, 6-9 week-old null mice show significantly less severe memory deficits than brain-injured wild-type controls based on performance scores in the Morris water maze
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• at 48 hours after CCI, both injured mutants and controls show significant motor deficits (neuroscores), but those in mutants are less severe than in injured wild-type mice
• at 1 week post-injury, mutants and wild-type mice with CCI display similar neuroscores, and by 3 weeks, wild-type mice show recovery of motor function to wild-type levels whereas Tnf-null injured mice do not display any significant recovery with time
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• brain-injured Tnf-null mice perform better than injured wild-type in balance beam and rotarod tests at 48 hours post-injury; by 3 weeks, wild-type mice show significant recovery to uninjured control levels while injured mutants display little recovery of function
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nervous system
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• by 1 week post-injury, brain-injured wild-type and Tnf-null mice display a well-developed cavity in ipsilateral cortex; at 4 weeks, in injured wild-type mice, cavity does not extend beyond cortex, but in mutants, cavity reaches white matter or may even become confluent with ventricle
• at 1 week, cavity volume is comparable between wild-type and null mice, but by 2 weeks post-injury, mutants show a greater cortical injury cavity volume than wild-type
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cellular
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• after bleomycin injection, fewer apoptotic inflammatory cells are seen in brochoalveolar lavage fluid (BALF) from Tnf-null lungs compared to wild-type BALF
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immune system
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• intratracheal injection of bleomycin induces infiltration of inflammatory cells in lungs; infiltration reaches peak at day 7 and decreases from that time point in wild-type, but treated mutants show persistent infiltration beyond day 7 to at least day 35 after injection
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respiratory system
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• intratracheal injection of bleomycin induces infiltration of inflammatory cells in lungs; infiltration reaches peak at day 7 and decreases from that time point in wild-type, but treated mutants show persistent infiltration beyond day 7 to at least day 35 after injection
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• Tnf-null lungs show significantly higher total cell and lymphocyte counts than wild-type at 21 days following intratracheal injection of bleomycin
• inflammatory changes (infiltration by lymphocytes, septal thickening of alveoli, and fibroblast proliferation) subside in wild-type mice by 75 days post-bleomycin treatment but severe infiltration and honeycomb-like structure are still observed in mutant lungs at this time
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Allelic
Composition |
Tnftm1Ljo/Tnftm1Ljo
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Genetic
Background |
either: B6.129-Tnftm1Ljo or (involves: 129 * C57BL/6) |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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immune system
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• neutrophil numbers are increased compared to Tnftm1.2Sned homozygotes
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• lymphocyte numbers are increased compared to Tnftm1.2Sned homozygotes
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• absent primary B cell follicles; however, follicle-associated epithelium and distribution of M cells are normal
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• mixed T and B cell zones
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• absent germinal centers
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• Peyer's patches are fewer in number
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• homozygotes are protected from LPS/D-Gal induced shock
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• homozygotes show increased sensitivity to systemic and alimentary L. monocytogenes infection
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hematopoietic system
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• neutrophil numbers are increased compared to Tnftm1.2Sned homozygotes
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• lymphocyte numbers are increased compared to Tnftm1.2Sned homozygotes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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HIstology of liver and spleen from C. parvum-treated wild type and Tnftm1Ljo/Tnftm1Ljo mice
immune system
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• absence of polarized B-cell follicles
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• mutants fail to develop germinal centers in the spleen following immunization with SRBC
(J:41992)
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• gradual reduction of white pulp size
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• mutants exhibit a deficiency in maturation of normal antibody response to T-cell dependent antigen (SRBC), showing depressed IgG titers but normal IgM titers
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• serum TNF levels are reduced in mutants injected with LPS and can not be detected on day 2 of Listeria monocytogenes infection
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• the normal uptake of aggregated gamma globulin by follicular dendritic cells in the spleen of immunized mutants is absent
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• production of colony-stimulating factor (CSF), specifically granulocyte-macrophage (GM)-CSF, is reduced after i.p. injection of lipopolysaccharide (LPS)
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• induction of MCP-1 is reduced in spleens of mutants infected with Listeria monocytogenes
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• increased resistance to liver injury after ConA-induced autoimmune hepatitis, with only infiltrating cells but no liver necrosis detected
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• mutants are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, however at higher concentrations (1200ug), they succumb to illness to the same extent as wild-type
(J:41992)
• mutants are resistant to staphylococcal enterotoxin B in the presence of D-gal
(J:41992)
• protected from S. aureus enterotoxin B induced toxic shock
(J:95684)
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• mutants show a delayed (40 days post injection instead of the 10-14 seen in wild-type), but progressive, response to heat-killed Corynebacterium parvum, that, unlike in wild-type, eventually leads to death by 80 days
(J:41992)
• increased susceptibility to Salmonella enterica infection
(J:80616)
• increased susceptibility to Listeria monocytogenes infections, with mutants dying by day 8 while wild-type mice survive
(J:80616)
• loss of resistance against Listeria monocytogenes
(J:95684)
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• mutants exhibit increased susceptibility to Candida albicans challenge; 100% die by day 7 post-infection
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hematopoietic system
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• absence of polarized B-cell follicles
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• mutants fail to develop germinal centers in the spleen following immunization with SRBC
(J:41992)
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• gradual reduction of white pulp size
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• mutants exhibit a deficiency in maturation of normal antibody response to T-cell dependent antigen (SRBC), showing depressed IgG titers but normal IgM titers
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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immune system
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• neutrophil numbers are similar in uninfected or infected (during first days of infection) wild-type controls and Tnftm2Jods homozygous mice
• 7 days post-infection, neutrophil cell number assessed by myeloperoxidase activity levels in footpad lesions relative to infected controls; higher percentage of neutrophils are detected in footpads after 7 days
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• 40 days post-infection, a higher percentage of neutrophils in lesion are apoptotic compared to infected controls
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• levels of IgG2a ins sera are undetectable in infected mutants compared to infected wild-type
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• mean percentage of IFN-gamma secreting CD4+ T cells is markedly enhanced (23.6%) in draining lymph nodes
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• cellularity is relatively lower than in wild-type C57BL/6 or Tnftm1Jods homozygous mice
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• lymph node cells release more IFN-gamma than wild-type cells
• Il-4 secretion upon re-stimulation with L. major is equivalent to wild-type
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• 60 days after L. major infection, mutants have much higher numbers of intralesional parasites than infected wild-type C57BL/6
• number of parasitized neutrophils in lesion is significantly higher in mutants than in infected controls 4 hours after i.p. injection of L.major; percentage of proliferating parasites released from neutrophils is significantly greater than seen in infected controls
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hematopoietic system
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• neutrophil numbers are similar in uninfected or infected (during first days of infection) wild-type controls and Tnftm2Jods homozygous mice
• 7 days post-infection, neutrophil cell number assessed by myeloperoxidase activity levels in footpad lesions relative to infected controls; higher percentage of neutrophils are detected in footpads after 7 days
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• 40 days post-infection, a higher percentage of neutrophils in lesion are apoptotic compared to infected controls
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• levels of IgG2a ins sera are undetectable in infected mutants compared to infected wild-type
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integument
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• mice infected with L. major promastigotes are unable to control developing footpad lesion size, exhibiting much larger lesion size than infected wild-type control at >35 days after infection
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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liver/biliary system
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N |
• mice fed a high cholesterol diet do not develop hepatic steatosis unlike Lta/Tnftm1Eug homozygotes
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Allelic
Composition |
Tnftm1Ljo/Tnf+
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Genetic
Background |
involves: 129S1/Sv |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
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immune system
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• exhibit increased susceptibility to high-dose LPS lethality
• exhibit delayed resolution of the Corynebacterium parvum induced inflammatory process lipopolysaccharide (LPS) lethality
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• exhibit increased susceptibility to Candida albicans challenge; 60% die by 30 days post-infection
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mortality/aging
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• triple homozygous pups die within 12 hours of birth
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• fewer than expected triple homozygous mutants are found at birth
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integument
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• the epidermis is marginally thinner
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mortality/aging
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• triple homozygous pups die within 12 hours of birth
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cellular
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• transit-amplifying epidermal cells display a delay in G1/S phase progression
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• transit-amplifying epidermal cells display reduced proliferation
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embryo
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• triple homozygous embryos are about 30% smaller compared to littermate controls
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growth/size/body
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• triple homozygous embryos are about 30% smaller compared to littermate controls
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integument
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• about a 24 hour delay in hair placode formation is seen compared to control littermates
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• at E18 the hair follicles that are present are only rudimentary buds lacking hair shafts
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• at E18, 70% fewer hair follicles are present compared to control littermates
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• the cells in the basal cell layer are organized differently and the basal cell profile area is reduced by about 33%
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• the number of differentiating keratinocytes is reduced
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• the epidermis is significantly thinner
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nervous system
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• Schwann cell apoptosis is increased compared to in wild-type mice 24 hours post-axotomy
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
Tnip1tm1.1Ama mutation
(0 available);
any
Tnip1 mutation
(55 available)
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mortality/aging
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N |
• mice are born in Mendelian ratio
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnftm1Ljo mutation
(3 available);
any
Tnf mutation
(46 available)
Tnip1tm1.1Ama mutation
(0 available);
any
Tnip1 mutation
(55 available)
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mortality/aging
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• fewer than expected mice are born alive
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muscle
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• myogenesis is accelerated in myoblasts in cultured mouse embryonic fibroblasts and in vivo
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• mice exhibit a decrease in fiber diameter
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• mutant mice exhibit a 76% increase in the number of myofibers
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Analysis Tools