Phenotypes associated with this allele

• Allele Symbol: Tnf^tm1Gkl
• Allele Name: targeted mutation 1, George Kollias
• Allele ID: MGI:2149024
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnf^tm1Gkl/Tnf^tm1Gkl	B6;129S-Tnf^tm1Gkl/J	MGI:4365459
hm2	Tnf^tm1Gkl/Tnf^tm1Gkl	C.129S-Tnf^tm1Gkl	MGI:4418571
hm3	Tnf^tm1Gkl/Tnf^tm1Gkl	either: B6.129-Tnf^tm1Gkl or (involves: 129 * C57BL/6)	MGI:3582276
hm4	Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv	MGI:3527264
hm5	Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * C57BL/6	MGI:2175016
hm6	Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * C57BL/6J	MGI:3722940
ht7	Tnf^tm1Gkl/Tnf^tm2Gkl	involves: 129S/SvEv * C57BL/6	MGI:3622062
cn8	Fadd^tm1Mpa/Fadd^tm1Mpa Tnf^tm1Gkl/Tnf^tm1Gkl Tg(Vil1-cre)997Gum/0	B6.Cg-Fadd^tm1Mpa Tnf^tm1Gkl Tg(Vil1-cre)997Gum	MGI:5293404
cx9	Timp3^tm1Rkho/Timp3^tm1Rkho Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129 * 129S/SvEv * C57BL/6	MGI:3664937
cx10	Krt8^tm1Rgo/Krt8^tm1Rgo Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * FVB/N	MGI:3711994
cx11	Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699099
cx12	Tnf^tm1Gkl/Tnf^tm1Gkl Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl	involves: 129S/SvEv * C57BL/6	MGI:3053734
cx13	Tnf^tm1Gkl/Tnf^tm1Gkl Zfp36^tm1Pjb/Zfp36^tm1Pjb	involves: 129S/SvEv * C57BL/6	MGI:5588803
cx14	Tnf^tm1Gkl/Tnf^tm1Gkl Tnfaip3^tm1Ama/Tnfaip3^tm1Ama	involves: 129S/SvEv * C57BL/6J	MGI:3055288

Genotype
MGI:4365459

hm1

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: B6;129S-Tnf^tm1Gkl/J

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

cellular

oligozoospermia ( J:143457 )

♂ • at 12 weeks of age, male homozygotes show a ~53% reduction in epididymal sperm count relative to wild-type controls

♂ • in mutant males, the number of sperm per testis weight is only ~68% that of wild-type controls

reproductive system

decreased testis weight ( J:143457 )

♂ • at 12 weeks of age, male homozygotes show a ~30% reduction in average testis weight relative to wild-type controls

abnormal testis physiology ( J:143457 )

♂ • after puberty (P30 to adulthood), mRNA levels of key steroidogenesis-related genes are significantly lower in mutant testes than in wild-type testes

decreased testes secretion ( J:143457 )

♂ • after puberty, male homozygotes display significantly lower testicular testosterone levels than wild-type males, as a result of higher anti-Mullerian hormone levels in mutant testes

abnormal spermatogenesis ( J:143457 )

♂ • male homozygotes show a significant delay in the onset of spermatogenesis, likely due to decreased testicular testosterone levels

♂ • at P26, the most advanced germ cells in mutant testes remain as late pachytene spermatocytes, instead of developing into haploid round spermatids as in wild-type testes

♂ • at P33, only early elongated spermatids are noted in mutant testes, whereas late elongated spermatids are seen in wild-type testes

oligozoospermia ( J:143457 )

♂ • at 12 weeks of age, male homozygotes show a ~53% reduction in epididymal sperm count relative to wild-type controls

♂ • in mutant males, the number of sperm per testis weight is only ~68% that of wild-type controls

abnormal spermiation ( J:143457 )

♂ • at P37, no sperm are yet detected in mutant epididymides

♂ • at P56, spermatozoa are detected at the luminal edge of seminiferous epithelia in both wild-type and mutant testes; however, the lumen is only dilated in wild-type tubules indicating active release of sperm

endocrine/exocrine glands

decreased testis weight ( J:143457 )

♂ • at 12 weeks of age, male homozygotes show a ~30% reduction in average testis weight relative to wild-type controls

abnormal testis physiology ( J:143457 )

♂ • after puberty (P30 to adulthood), mRNA levels of key steroidogenesis-related genes are significantly lower in mutant testes than in wild-type testes

decreased testes secretion ( J:143457 )

♂ • after puberty, male homozygotes display significantly lower testicular testosterone levels than wild-type males, as a result of higher anti-Mullerian hormone levels in mutant testes

Genotype
MGI:4418571

hm2

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: C.129S-Tnf^tm1Gkl

neoplasm

decreased incidence of tumors by chemical induction ( J:56068 )

• DMBA and TPA-treated mice exhibit papillomas than in similarly treated wild-type mice

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:56068 )

• DMBA and TPA-treated mice exhibit papillomas than in similarly treated wild-type mice

Genotype
MGI:3582276

hm3

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: either: B6.129-Tnf^tm1Gkl or (involves: 129 * C57BL/6)

immune system

increased leukocyte cell number ( J:97783 )

• a modest increase in peripheral white cell count is seen compared to wild-type mice

increased neutrophil cell number ( J:97783 )

• neutrophil numbers are increased compared to Tnf^tm1.2Sned homozygotes

increased lymphocyte cell number ( J:97783 )

• lymphocyte numbers are increased compared to Tnf^tm1.2Sned homozygotes

decreased Peyer's patch number ( J:97783 )

• Peyer's patches are fewer in number

small Peyer's patches ( J:97783 )

decreased susceptibility to bacterial infection ( J:97783 )

• homozygotes are protected from LPS/D-Gal induced shock

increased susceptibility to parasitic infection ( J:97783 )

• homozygotes show increased sensitivity to systemic and alimentary L. monocytogenes infection

hematopoietic system

increased leukocyte cell number ( J:97783 )

• a modest increase in peripheral white cell count is seen compared to wild-type mice

increased neutrophil cell number ( J:97783 )

• neutrophil numbers are increased compared to Tnf^tm1.2Sned homozygotes

increased lymphocyte cell number ( J:97783 )

• lymphocyte numbers are increased compared to Tnf^tm1.2Sned homozygotes

Genotype
MGI:3527264

hm4

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv

immune system

decreased circulating tumor necrosis factor level ( J:95684 )

• serum TNF levels were reduced in mutants injected with LPS and could not be detected on day 2 of Listeria monocytogenes infection

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, with only infiltrating cells but no liver necrosis detected

decreased susceptibility to endotoxin shock ( J:95684 )

• protected from S. aureus enterotoxin B induced toxic shock

increased susceptibility to bacterial infection ( J:95684 )

• loss of resistance against Listeria monocytogenes infection

homeostasis/metabolism

decreased circulating tumor necrosis factor level ( J:95684 )

• serum TNF levels were reduced in mutants injected with LPS and could not be detected on day 2 of Listeria monocytogenes infection

Genotype
MGI:2175016

hm5

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

alveolar process atrophy ( J:147935 )

• modest alveolar bone loss at 30 weeks

decreased body weight ( J:42579 )

• at 28 weeks, mutant animals weigh less

adipose tissue

abnormal fat pad morphology ( J:42579 )

decreased percent body fat/body weight ( J:42579 )

homeostasis/metabolism

decreased circulating leptin level ( J:42579 )

• decreased plasma leptin concentrations at 28 weeks of age

abnormal glucose homeostasis ( J:42579 )

decreased circulating glucose level ( J:42579 )

• decreased fasting plasma glucose concentrations at 28 weeks of age

decreased circulating insulin level ( J:42579 )

• decreased plasma insulin concentrations at 28 weeks of age

abnormal lipid homeostasis ( J:42579 )

decreased circulating triglyceride level ( J:42579 )

• decreased plasma triglyceride concentrations at 28 weeks of age

decreased incidence of tumors by chemical induction ( J:56068 )

• DMBA and TPA-treated mice exhibit papillomas that develop with a greater latency than in similarly treated wild-type mice DMBA and TPA-treated mice exhibit papillomas that develop with a greater latency than in similarly treated wild-type mice however, malignant progression of tumors is normal

• however, malignant progression of tumors is normal

immune system

immune system phenotype ( J:114740 )

N • mutant spleen cells isolated 49 days after myelin oligodendrocyte glycoprotein (MOG) display lack of autoimmune T cell responses (proliferation) to MOG peptide, similar to wild-type spleen cells

abnormal spleen follicular dendritic cell network ( J:42579 )

• organized follicular dendritic cell networks are absent

abnormal spleen primary B follicle morphology ( J:47673 )

• absence of splenic primary B cell follicles

absent spleen germinal center ( J:47673 , J:114740 )

• inability to form organized germinal centers (J:47673)

• after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers (J:114740)

abnormal lymphocyte physiology ( J:114740 )

• after intraperitoneal injection of SRBC, mutants exhibit severely impaired SRBC-specific IgG1 antibody responses

abnormal macrophage physiology ( J:114740 )

• LPS-stimulated thioglycollate-elicited peritoneal macrophages (TEPMs) cannot induce thymocyte proliferation, but stimulated TEPMs in wild-type and Tnf^tm3Gki homozygotes induce thymocyte proliferation with equal efficiency

absent follicular dendritic cells ( J:40970 )

• organized follicular dendritic cell networks are absent

abnormal Peyer's patch morphology ( J:40970 )

• the typical subepithelial dome areas fail to form

abnormal Peyer's patch follicle morphology ( J:40970 )

• B cells are present but no organized follicles are seen and organized follicular dendritic cell networks are absent

decreased Peyer's patch number ( J:40970 )

• average of 2 - 4 per mouse compared to 6 - 8 in wild-type mice

abnormal mesenteric lymph node morphology ( J:114740 )

• mesenteric lymph nodes (MLN) lack organized B cell follicles but occasionally have GC-like regions that are centered in B cell areas

abnormal lymph node B cell domain morphology ( J:40970 )

• B cell follicles and follicular dendritic cell network formation are impaired in mesenteric and peripheral lymph nodes; however, B cells are present and B and T cell areas are segregated

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:114740 )

• 16 days post-immunization with pertussis toxin, mutants begin to show clinical signs of experimental allergic encephalomyelitis (EAE) which progresses to chronic non-remitting disease compared to wild-type mice which show signs of EAE at 12 days post-injectiona and peak EAE occurs at ~15 days, with gradual remission and results in only a mild deficit

abnormal inflammatory response ( J:114740 )

• when treated with D-gal (a hepatotoxin) at 20 mg/animal and doses of lipopolysaccharide (LPS) up to 100ug/25g body weight, mutants are completely resistant to LPS-induced death, but wild-type mice all die at 100-fold lower LPS doses

decreased inflammatory response ( J:56068 )

• in the skin following treatment with TPA compared with similarly treated wild-type mice

decreased susceptibility to type IV hypersensitivity reaction ( J:47673 )

• impaired contact hypersensitivity response

increased susceptibility to bacterial infection ( J:47673 , J:114740 )

• susceptibility to death from Listeria monocytogenes infection (J:47673)

• with challenge at high doses (10000 cfu) of Listeria monocytogenes (LM), mutants show high sensitivity with maximal lethality at 6 days post-infection, compared to wild-type; mutants are highly sensitive when challenged with a physiological dose of LM (100 cfu) compared to wild-type (J:114740)

hematopoietic system

abnormal spleen follicular dendritic cell network ( J:42579 )

• organized follicular dendritic cell networks are absent

abnormal spleen primary B follicle morphology ( J:47673 )

• absence of splenic primary B cell follicles

absent spleen germinal center ( J:47673 , J:114740 )

• inability to form organized germinal centers (J:47673)

• after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers (J:114740)

abnormal lymphocyte physiology ( J:114740 )

• after intraperitoneal injection of SRBC, mutants exhibit severely impaired SRBC-specific IgG1 antibody responses

abnormal macrophage physiology ( J:114740 )

• LPS-stimulated thioglycollate-elicited peritoneal macrophages (TEPMs) cannot induce thymocyte proliferation, but stimulated TEPMs in wild-type and Tnf^tm3Gki homozygotes induce thymocyte proliferation with equal efficiency

neoplasm

decreased incidence of tumors by chemical induction ( J:56068 )

• DMBA and TPA-treated mice exhibit papillomas that develop with a greater latency than in similarly treated wild-type mice DMBA and TPA-treated mice exhibit papillomas that develop with a greater latency than in similarly treated wild-type mice however, malignant progression of tumors is normal

• however, malignant progression of tumors is normal

craniofacial

alveolar process atrophy ( J:147935 )

• modest alveolar bone loss at 30 weeks

skeleton

alveolar process atrophy ( J:147935 )

• modest alveolar bone loss at 30 weeks

increased bone mineral density ( J:135519 )

• significantly increased

increased osteoblast cell number ( J:135519 )

abnormal trabecular bone morphology ( J:135519 )

• 32% increase in trabecular bone volume

integument

decreased keratinocyte proliferation ( J:56068 )

• following DMBA and TPA treatment compared with similarly treated wild-type mice

cellular

decreased keratinocyte proliferation ( J:56068 )

• following DMBA and TPA treatment compared with similarly treated wild-type mice

Genotype
MGI:3722940

hm6

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * C57BL/6J

immune system

abnormal metallophilic macrophage morphology ( J:124642 )

• there are almost no metallophillic macrophages present in the marginal zone

abnormal spleen follicular dendritic cell network ( J:124642 )

• upon immunization with a T cell dependent antigen, there is a no formation of a follicular dendritic cell network

abnormal spleen primary B follicle morphology ( J:124642 )

• B cells fail to form a defined primary follicle instead forming a ring-like structure that is partially mixed with the T cell region

absent spleen germinal center ( J:124642 )

• upon immunization with T cell dependent antigen, germinal centers fail to develop

abnormal spleen marginal sinus morphology ( J:124642 )

• marginal sinus lining cells expressing mucosal addressin cell adhesion molecules are not present when immunized with a T cell antigen

abnormal Peyer's patch morphology ( J:124642 )

• Peyer's patches have a flattened appearance

abnormal Peyer's patch follicle morphology ( J:124642 )

• B cells fail to segregate from T cell areas

abnormal Peyer's patch T cell area morphology ( J:124642 )

• T cells fail to segregate from B cells

abnormal Peyer's patch germinal center morphology ( J:124642 )

• upon immunization with a T cell dependent antigen, germinal centers fail to develop

decreased Peyer's patch number ( J:124642 )

• the mean number of Peyer's patches in mutant mice is 5 compared to 7 in wild-type mice

increased susceptibility to bacterial infection ( J:124642 )

• 7 days after a sublethal dose of Listeria monocytogenes, no mice survive compared to 60% survival of wild-type mice

hematopoietic system

abnormal metallophilic macrophage morphology ( J:124642 )

• there are almost no metallophillic macrophages present in the marginal zone

abnormal spleen follicular dendritic cell network ( J:124642 )

• upon immunization with a T cell dependent antigen, there is a no formation of a follicular dendritic cell network

abnormal spleen primary B follicle morphology ( J:124642 )

• B cells fail to form a defined primary follicle instead forming a ring-like structure that is partially mixed with the T cell region

absent spleen germinal center ( J:124642 )

• upon immunization with T cell dependent antigen, germinal centers fail to develop

abnormal spleen marginal sinus morphology ( J:124642 )

• marginal sinus lining cells expressing mucosal addressin cell adhesion molecules are not present when immunized with a T cell antigen

Genotype
MGI:3622062

ht7

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm2Gkl
• Genetic Background: involves: 129S/SvEv * C57BL/6

immune system

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice

increased tumor necrosis factor secretion ( J:54056 )

• increased basal and LPS-induced secretion of TNF from thioglycollate-elicited peritoneal macrophages and bone marrow-derived macrophages

• spleen derived T lymphocytes have 3-fold greater TNF production and prolonged mRNA accumulation after incubation with an agonistic anti-CD3 antibody

• splenic B220+ cells also show increased basal and mitogen-stimulated TNF production

• primary synovial and lung fibroblasts display spontaneous TNF secretion and increased secretion following LPS stimulation unlike controls

rheumatoid arthritis ( J:54056 )

• disease onset occurs at 6-8 weeks of age

• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction

• both IgM and IgG are detected in arthritic joints

increased susceptibility to endotoxin shock ( J:54056 )

• increased sensitivity to LPS-induced mortality with 5 of 10 dying after injection of 100 ug/ 25 g compared to complete survival of control mice at the same dose

skeleton

rheumatoid arthritis ( J:54056 )

• disease onset occurs at 6-8 weeks of age

• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction

• both IgM and IgG are detected in arthritic joints

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:54056
rheumatoid arthritis		DOID:7148	OMIM:180300	J:54056

Genotype
MGI:5293404

cn8

• Allelic Composition: Fadd^tm1Mpa/Fadd^tm1Mpa; Tnf^tm1Gkl/Tnf^tm1Gkl; Tg(Vil1-cre)997Gum/0
• Genetic Background: B6.Cg-Fadd^tm1Mpa Tnf^tm1Gkl Tg(Vil1-cre)997Gum

digestive/alimentary system

decreased Paneth cell number ( J:175865 )

• reduced numbers

cecum inflammation ( J:175865 )

colitis ( J:175865 )

• less severe than in Fadd^tm1Mpa/Fadd^tm1Mpa Tg(Vil-cre)997Gum mice

endocrine/exocrine glands

decreased Paneth cell number ( J:175865 )

• reduced numbers

immune system

cecum inflammation ( J:175865 )

colitis ( J:175865 )

• less severe than in Fadd^tm1Mpa/Fadd^tm1Mpa Tg(Vil-cre)997Gum mice

Genotype
MGI:3664937

cx9

• Allelic Composition: Timp3^tm1Rkho/Timp3^tm1Rkho; Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6

cardiovascular system

dilated heart left ventricle ( J:112033 )

• double mutants subjected to cardiac pressure overload show a greater increase in left ventricle dilation after 3 weeks than wildtype but less than seen in single Timp3 homozygous mutants

decreased ventricle muscle contractility ( J:112033 )

• double mutants subjected to cardiac pressure overload show a greater decline in cardiac contractility than wild-type but not as much as single Timp3 homozygous mutants

hematopoietic system

increased neutrophil cell number ( J:112033 )

• myocardium of double mutants subjected to cardiac pressure overload contains significantly higher numbers of neutrophils scattered throughout the left ventricle compared with single homozygous Timp3 mutants or wild-type

immune system

increased neutrophil cell number ( J:112033 )

• myocardium of double mutants subjected to cardiac pressure overload contains significantly higher numbers of neutrophils scattered throughout the left ventricle compared with single homozygous Timp3 mutants or wild-type

muscle

decreased ventricle muscle contractility ( J:112033 )

• double mutants subjected to cardiac pressure overload show a greater decline in cardiac contractility than wild-type but not as much as single Timp3 homozygous mutants

Genotype
MGI:3711994

cx10

• Allelic Composition: Krt8^tm1Rgo/Krt8^tm1Rgo; Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:121811 )

N • about 60% survive beyond 250 days

prenatal lethality, incomplete penetrance ( J:121811 )

• Background Sensitivity: about 50% survive to birth as opposed to 25% when maternal TNF is produced

Genotype
MGI:3699099

cx11

• Allelic Composition: Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro; Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * BALB/cJ * C57BL/6J

skeleton

skeleton phenotype ( J:117880 )

N • unlike in mice homozygous for the Sh3bp2 allele alone, trabecular and cortical bone loss are not seen

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

immune system

immune system phenotype ( J:117880 )

N • unlike in mice homozygous for the Sh3bp2 allele alone, lymph node abnormalities and systemic inflammation are not seen

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

cellular

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	cherubism	DOID:1856	OMIM:118400	J:117880

Genotype
MGI:3053734

cx12

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl; Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl
• Genetic Background: involves: 129S/SvEv * C57BL/6

immune system

immune system phenotype ( J:92470 )

N • no liver inflammation is seen unlike in Tnfrsf1a^tm1Gkl homozygotes

Genotype
MGI:5588803

cx13

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl; Zfp36^tm1Pjb/Zfp36^tm1Pjb
• Genetic Background: involves: 129S/SvEv * C57BL/6

cardiovascular system

abnormal vasodilation ( J:214114 )

• mice do not show improvement of the endothelial dysfunction seen in single Zfp36 homozygotes, with aortas still less responsive to acetylcholine-induced relaxation

cellular

oxidative stress ( J:214114 )

• mice show a partial reduction of the enhanced reactive oxygen and nitrogen species (RONS) formation under PDBu-stimulated conditions in whole blood that is seen in single Zfp36 homozygotes

muscle

abnormal vasodilation ( J:214114 )

• mice do not show improvement of the endothelial dysfunction seen in single Zfp36 homozygotes, with aortas still less responsive to acetylcholine-induced relaxation

Genotype
MGI:3055288

cx14

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm1Gkl; Tnfaip3^tm1Ama/Tnfaip3^tm1Ama
• Genetic Background: involves: 129S/SvEv * C57BL/6J

mortality/aging

premature death ( J:92694 )

growth/size/body

cachexia ( J:92694 )

immune system

abnormal cytokine secretion ( J:92694 )

• bone marrow derived macrophages produce more IL-6 and nitric oxide in response to LPS treatment compared to Tnfaip1^tm1Ama heterozygous Tnf^tm1Gkl homozygous macrophages

abnormal inflammatory response ( J:92694 )

• the absolute number and percentage of myeloid cells is increased in multiple tissues