Phenotypes associated with this allele

• Allele Symbol: Tlr3^tm1Flv
• Allele Name: targeted mutation 1, Richard A Flavell
• Allele ID: MGI:2653138
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlr3^tm1Flv/Tlr3^tm1Flv	B6.129S1-Tlr3^tm1Flv/Apb	MGI:5013822
hm2	Tlr3^tm1Flv/Tlr3^tm1Flv	B6N.129S1-Tlr3^tm1Flv/J	MGI:6433074
hm3	Tlr3^tm1Flv/Tlr3^tm1Flv	involves: 129S1/Sv	MGI:5013821
hm4	Tlr3^tm1Flv/Tlr3^tm1Flv	involves: 129S1/Sv * C57BL/6	MGI:2653141
hm5	Tlr3^tm1Flv/Tlr3^tm1Flv	involves: C57BL/6	MGI:3033874
hm6	Tlr3^tm1Flv/Tlr3^tm1Flv	Not Specified	MGI:3039447
cx7	Smcr8^em1Btlr/Smcr8^em1Btlr Tlr3^tm1Flv/Tlr3^tm1Flv Tlr7^tm1Aki/Tlr7^tm1Aki Tlr9^tm1Aki/Tlr9^tm1Aki	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6J	MGI:6272653

Genotype
MGI:5013822

hm1

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: B6.129S1-Tlr3^tm1Flv/Apb

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

homeostasis/metabolism

abnormal cytokine level ( J:129533 )

• reduced cytokine response 8 hours after poly I:C treatment as determined by TNF alpha, IL-6, IL12p40, and IFN-beta

abnormal interleukin level ( J:126415 )

• IL-13 is upregulated in the lungs after infection with Respiratory syncytial virus

• IL-5 is upregulated later in the infection response to Respiratory syncytial virus

delayed wound healing ( J:169762 )

• wound healing of full thickness circular skin opennings are markedly delayed

• full wound closure around 14 days rather than 12 days as in controls

• reduced infiltration of neutrophiles at days 1 and 3 and of macrophage at days 3 and 6

• reduced presence of chemokines involved in leukocyte recruitment

respiratory system

abnormal respiratory system physiology ( J:126415 )

• increased mucus in the lungs 6 days after infection

• antibody to IL13 attenuates the mucus response to Respiratory syncytial virus

nervous system

abnormal axon morphology ( J:127638 )

• number of axons in L1-L5 dorsal roots is unaffected by poly I:C treatment, unlike controls

abnormal neuron physiology ( J:127638 )

• isolated E14 dorsal root ganglion neurons are resistant to poly I:C inhibition of neurite outgrowth

behavior/neurological

abnormal righting response ( J:127638 )

• treatment of mice at 4 days of age has no effect on righting behavior at 9 days of age, unlike controls

neoplasm

increased tumor incidence ( J:158910 )

• implanted tumor cells grow larger than in controls

immune system

abnormal cytokine level ( J:129533 )

• reduced cytokine response 8 hours after poly I:C treatment as determined by TNF alpha, IL-6, IL12p40, and IFN-beta

abnormal interleukin level ( J:126415 )

• IL-13 is upregulated in the lungs after infection with Respiratory syncytial virus

• IL-5 is upregulated later in the infection response to Respiratory syncytial virus

decreased interferon-beta secretion ( J:251008 )

• in peritoneal macrophages stimulated with poly(I:C)

Genotype
MGI:6433074

hm2

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: B6N.129S1-Tlr3^tm1Flv/J

immune system

increased susceptibility to Coronaviridae infection ( J:288471 )

• mice infected intranasally with the mouse-adapted rMA15-SARS-CoV show greater weight loss, increased viral titers in the lungs, increased lung function impairment and lung pathology

• viral titers in the lungs of rMA15-SARS-CoV-infected mice are increased 4-fold at 2 days post-infection (dpi), 20-fold at 4 dpi, and still detectable on 7 dpi, a time by which the virus is cleared in wild-type mice

respiratory system

abnormal respiratory function ( J:288471 )

• rMA15-SARS-CoV-infected mice show impaired lung function

Genotype
MGI:5013821

hm3

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: involves: 129S1/Sv

mortality/aging

decreased susceptibility to Riboviria infection induced morbidity/mortality ( J:136330 )

• in mice infected with rabies virus

increased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:119967 )

• decreased survival after infection with Encephalomyocarditis virus

• severe decline in survival of both homozygotes and heterozygotes after 3 days

• homozygote deaths continue for 141 days after infection while control and heterozygote deaths level off after 8-10 days

• higher viral titers in the heart

cardiovascular system

heart inflammation ( J:119967 )

• higher viral titers of Encephalomyocarditis virus in the hearts of homozygotes

• less mononuclear cell and T cell infiltration of the myocardium at 3 and 5 days after infection

homeostasis/metabolism

hyperglycemia ( J:135353 )

• higher glycemia in the fed state but normal glucose tolerance

increased circulating troponin I level ( J:119967 )

• serum levels of cardiac troponin I are elevated indicating myocardial damage

abnormal cytokine level ( J:119967 )

abnormal interferon level ( J:119967 )

• IFN-beta expression is augmented 3 days after infection

abnormal interleukin level ( J:119967 )

• expression of IL1beta is delayed until 5 days after infection

• change in expression is due at least in part due to expression in myocytes

abnormal tumor necrosis factor level ( J:119967 )

• expression is delayed until 5 days after infection

• change in expression is due at least in part due to expression in myocyte

immune system

heart inflammation ( J:119967 )

• higher viral titers of Encephalomyocarditis virus in the hearts of homozygotes

• less mononuclear cell and T cell infiltration of the myocardium at 3 and 5 days after infection

abnormal cytokine level ( J:119967 )

abnormal interferon level ( J:119967 )

• IFN-beta expression is augmented 3 days after infection

abnormal interleukin level ( J:119967 )

• expression of IL1beta is delayed until 5 days after infection

• change in expression is due at least in part due to expression in myocytes

abnormal tumor necrosis factor level ( J:119967 )

• expression is delayed until 5 days after infection

• change in expression is due at least in part due to expression in myocyte

increased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:119967 )

• decreased survival after infection with Encephalomyocarditis virus

• severe decline in survival of both homozygotes and heterozygotes after 3 days

• homozygote deaths continue for 141 days after infection while control and heterozygote deaths level off after 8-10 days

• higher viral titers in the heart

decreased susceptibility to Riboviria infection ( J:136330 )

• mice infected with rabies virus exhibit improved survival compared with wild-type mice

decreased susceptibility to Riboviria infection induced morbidity/mortality ( J:136330 )

• in mice infected with rabies virus

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:148283 )

decreased pancreatic beta cell mass ( J:148283 )

• slightly decreased beta cell mass although the percent volume is increased

increased pancreatic islet number ( J:148283 )

abnormal pancreatic beta cell physiology ( J:135353 )

• isolated beta cells are resistant to apoptosis induced by dsRNA and IFN-gamma or induced by dsRNA and lipofectamine

• insulin content of beta cells is unaffected by ds RNA whereas content decreases

reproductive system

abnormal pregnancy ( J:164980 )

♀ • intraperitoneal injection of poly I:C fails to induce preterm delivery as it does in controls

abnormal postimplantation uterine environment ( J:164980 )

♀ • no placental necrosis, hemorrhage or edema after intraperitoneal injection of poly I:C

♀ • trophoblast fails to secrete cytokines in response to intraperitoneal injection of poly I:C

Genotype
MGI:2653141

hm4

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

immune system phenotype ( J:72167 )

N • normal lymphocyte development

N • normal expression of CD3, B220, CD4, and CD8 in thymocytes and splenocytes

abnormal B cell physiology ( J:72167 )

• impaired expression of CD69, CD80, and CD86 in response to poly(I:C), but not LPS

• impaired expression of CD69 in response to viral genomic dsRNA from Type I Lang mammalian reovirus

abnormal macrophage physiology ( J:72167 )

• impaired ability to produce IL6, IL12 and TNF-alpha in response to poly(I:C), a synthetic dsRNA analogue

• production of IL6, IL12, and TNF-alpha in response to LPS, PGN, LTA, zymosan, mannan, or CpG DNA was comparable to wild-type controls

decreased inflammatory response ( J:72167 )

• resistant to poly(I:C)-induced shock compared to wild-type mice

• produced less IL12 after poly(I:C) i.p. injection

behavior/neurological

abnormal learning/memory/conditioning ( J:163748 )

abnormal long-term spatial reference memory ( J:163748 )

• retain memory of platform location in Morris maze tests up to 120 hours compared to 72 hours in controls

abnormal spatial working memory ( J:163748 )

• enhanced working memory

abnormal emotion/affect behavior ( J:163748 )

decreased anxiety-related response ( J:163748 )

• in open field tests and elevated + mazes

abnormal fear-related response ( J:163748 )

decreased fear-related response ( J:163748 )

• less cued fear response to a tone

increased fear-related response ( J:163748 )

• greater hippocampus dependent contextual fear response, freezing times

abnormal response to novel object ( J:163748 )

• increased interest in novel objects

impaired coordination ( J:163748 )

• poorer rotarod performance and motor learning

nervous system

abnormal hippocampus development ( J:163748 )

• increased hippocampal neurogenesis

abnormal hippocampus CA1 region morphology ( J:163748 )

• increased in volume

abnormal dentate gyrus morphology ( J:163748 )

• increased in volume

cardiovascular system

abnormal vascular wound healing ( J:169238 )

• protective effect of poly I:C on neointimal formation is lost

homeostasis/metabolism

abnormal vascular wound healing ( J:169238 )

• protective effect of poly I:C on neointimal formation is lost

hematopoietic system

abnormal B cell physiology ( J:72167 )

• impaired expression of CD69, CD80, and CD86 in response to poly(I:C), but not LPS

• impaired expression of CD69 in response to viral genomic dsRNA from Type I Lang mammalian reovirus

abnormal macrophage physiology ( J:72167 )

• impaired ability to produce IL6, IL12 and TNF-alpha in response to poly(I:C), a synthetic dsRNA analogue

• production of IL6, IL12, and TNF-alpha in response to LPS, PGN, LTA, zymosan, mannan, or CpG DNA was comparable to wild-type controls

Genotype
MGI:3033874

hm5

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: involves: C57BL/6

immune system

immune system phenotype ( J:86617 )

N • upregulation of costimulatory molecules, CD40 and CD86, by peritoneal macrophages in response to dsRNA was preserved on this background

abnormal macrophage physiology ( J:86617 )

• impaired ability to produce type I interferon and TNF-alpha in response to dsRNA, but not in response to LPS

hematopoietic system

abnormal macrophage physiology ( J:86617 )

• impaired ability to produce type I interferon and TNF-alpha in response to dsRNA, but not in response to LPS

Genotype
MGI:3039447

hm6

• Allelic Composition: Tlr3^tm1Flv/Tlr3^tm1Flv
• Genetic Background: Not Specified

immune system

abnormal NK cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

abnormal NK T cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

abnormal cytokine secretion ( J:88906 )

• type 1 IFN, IFNgamma and IL-12 p40 levels are decreased compared to C57BL/6 wild-type controls following sublethal viral infection, however this decrease is not as pronounced as in Myd88^tm1Aki homozygotes

increased susceptibility to Herpesvirales infection ( J:88906 )

• viral loads are significantly higher after mouse cytomegalovirus infection compared to C57BL/6 wild-type controls, however titers are not as high as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

hematopoietic system

abnormal NK cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

abnormal NK T cell physiology ( J:88906 )

• NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9^CpG1 or Myd88^tm1Aki homozygotes

Genotype
MGI:6272653

cx7

• Allelic Composition: Smcr8^em1Btlr/Smcr8^em1Btlr; Tlr3^tm1Flv/Tlr3^tm1Flv; Tlr7^tm1Aki/Tlr7^tm1Aki; Tlr9^tm1Aki/Tlr9^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6J

immune system

immune system phenotype ( J:268243 )

N • unlike in Smcr8^em1Btlr homozygotes, spleen and lymph nodes are restored to normal as well as is the hyperactivation of T cells and increased circulating IL12p40 levels