All Phenotypes Tlr2<tm1Aki> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlr2^tm1Aki/Tlr2^tm1Aki	B6.129P2-Tlr2^tm1Aki	MGI:3696116
hm2	Tlr2^tm1Aki/Tlr2^tm1Aki	C.129P2-Tlr2^tm1Aki	MGI:5297117
hm3	Tlr2^tm1Aki/Tlr2^tm1Aki	involves: 129P2/OlaHsd	MGI:3698170
hm4	Tlr2^tm1Aki/Tlr2^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:2178678
hm5	Tlr2^tm1Aki/Tlr2^tm1Aki	NOD.129P2-Tlr2^tm1Aki	MGI:4942396
cx6	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr4^tm1Aki/Tlr4^tm1Aki	B6.129P2-Tlr2^tm1Aki Tlr4^tm1Aki	MGI:3625114
cx7	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr4^tm1Aki/Tlr4^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:3707238
cx8	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr6^tm1Aki/Tlr6^tm1Aki	involves: 129P2/OlaHsd * C57BL/6	MGI:4456174

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki
Genetic Background	B6.129P2-Tlr2^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)

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

behavior/neurological

behavior/neurological phenotype ( J:247895 )

N	• mice exhibit normal behavior in elevated zero maze and open field assays

abnormal locomotor activation ( J:247895 )

• mice exhibit fewer daily active/inactive states, lower active/inactive state transitions but longer active/inactive state durations compared with wild-type C57BL/6 mice

• however, behavioral differences arent observed at 8-8.5 months of age

abnormal circadian behavior ( J:247895 )

• at 4-4.5 months of age, mice exhibit light cycle less movement, feeding and drinking compared with wild-type C57BL/6 mice and spend less time doing these activities

• at 4-4.5 months of age, mice exhibit increased state stability with fewer transitions between active and inactive states throughout the circadian day compared with wild-type C57BL/6

• at 4-4.5 months of age, mice exhibit fewer transitions between active/inactive states during the circadian light cycle compared with wild-type C57BL/6 mice

• at 4-4.5 months of age but less so at 8-8.5 months, mice exhibit less variability in circadian patterns of movement, feeding and drinking compared with wild-type C57BL/6 mice

• however, behavioral differences arent observed at 8-8.5 months of age

abnormal locomotor circadian rhythm ( J:247895 )

• reduced light cycle movement at 4-4.5 months of age

immune system

increased T cell number ( J:118954 )

• following infection with attenuated yellow fever vaccine 17D (YF-17D), the frequency of CD8+IFN-gamma+ T cells at day 10 is increased to 3.63% compared to 1.05% in wild-type mice

abnormal interleukin level ( J:118954 )

• Il-4 and IL-5 levels are increased

abnormal dendritic cell physiology ( J:118954 )

• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40 and IL-6 relative to wild-type mice

decreased interleukin-12b secretion ( J:118954 )

• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40 and IL-6 relative to wild-type mice

decreased interleukin-6 secretion ( J:118954 )

• following infection with attenuated yellow fever vaccine 17D (YF-17D), dendritic cells produce less IL-12p40 and IL-6 relative to wild-type mice

decreased susceptibility to parasitic infection ( J:116763 )

• resistant to cerebral malaria

• reduced accumulation of hemozoin

hematopoietic system

increased T cell number ( J:118954 )

• following infection with attenuated yellow fever vaccine 17D (YF-17D), the frequency of CD8+IFN-gamma+ T cells at day 10 is increased to 3.63% compared to 1.05% in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:247895 )

N	• mice exhibit normal metabolic parameters

abnormal circulating lipid level ( J:158035 )

• fasting serum triglycerides are reduced on a high fat diet

abnormal circulating cholesterol level ( J:158035 )

• serum cholesterol levels at 5 weeks on a high fat diet are similar to controls

abnormal circulating LDL cholesterol level ( J:158035 )

• levels do not increase on a high fat diet

decreased circulating VLDL cholesterol level ( J:158035 )

increased circulating free fatty acids level ( J:158035 )

• slightly elevated regardless of diet

abnormal glucose homeostasis ( J:158035 )

abnormal circulating glucose level ( J:158035 )

• fasting serum glucose is not elevated at 14 weeks on a high fat diet as it is in controls

abnormal circulating insulin level ( J:158035 )

• serum insulin levels remain normal at 14 weeks on a high fat diet

abnormal interleukin level ( J:118954 )

• Il-4 and IL-5 levels are increased

decreased cerebral infarct size ( J:122281 )

• considerably reduced infarct volume after 1 hour of cerebral ischemia and 2 days of reperfusion

decreased susceptibility to kidney reperfusion injury ( J:101532 )

• reduced granulocyte chemotactic keratinocyte chemoattractant and monocyte chemoattractant protein-1 in kidneys 1 day after ischemia/reperfusion injury relative to controls

• fewer interstitial infiltrated granulocytes relative to controls at 1 day after injury but not at 5 and 10 days

• macrophage infiltration of the outer medulla peaks at 5 days

• less apoptosis of kidney tubular endothelial cells than in controls after injury

• less regeneration after injury than in controls after reperfusion injury

respiratory system

decreased lung tumor incidence ( J:143870 )

• fewer and smaller tumor nodules develop in the lung after injection with Lewis lung carcinoma cells

abnormal respiratory system physiology ( J:98456 , J:147534 )

• Mycoplasma pneumoniae infection fails to induce mucin protein production in airways as occurs in controls (J:98456)

• bronchoalveolar protein levels are increased by ozone exposure (J:147534)

• ozone induced increase in bronchoalveolar cell counts is less than in controls at 3 hours but not 24 hours (J:147534)

abnormal airway responsiveness ( J:147534 )

• ozone exposure does not lead to hyperresponsiveness

neoplasm

decreased liver tumor incidence ( J:143870 )

• fewer liver tumors after injection with Lewis lung carcinoma cells

decreased lung tumor incidence ( J:143870 )

• fewer and smaller tumor nodules develop in the lung after injection with Lewis lung carcinoma cells

renal/urinary system

decreased susceptibility to kidney reperfusion injury ( J:101532 )

• reduced granulocyte chemotactic keratinocyte chemoattractant and monocyte chemoattractant protein-1 in kidneys 1 day after ischemia/reperfusion injury relative to controls

• fewer interstitial infiltrated granulocytes relative to controls at 1 day after injury but not at 5 and 10 days

• macrophage infiltration of the outer medulla peaks at 5 days

• less apoptosis of kidney tubular endothelial cells than in controls after injury

• less regeneration after injury than in controls after reperfusion injury

nervous system

abnormal neuron differentiation ( J:129957 )

• reduced differentiation of progenitor cells into neurons

decreased cerebral infarct size ( J:122281 )

• considerably reduced infarct volume after 1 hour of cerebral ischemia and 2 days of reperfusion

abnormal astrocyte morphology ( J:129957 )

• differentiation of progenitor cells into astrocytes is improved

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:148283 )

• beta cell volume as a percentage of pancreas volume is significantly reduced

small pancreatic islets ( J:148283 )

• islet size is reduced

• number of islets is normal

adipose tissue

abnormal body fat mass ( J:158035 )

• do not develop increased adiposity on a high fat diet

abnormal white fat cell size ( J:158035 )

• more moderate in size and with fewer associated leukocytes

growth/size/body

growth/size/body region phenotype ( J:158035 )

N	• lean body mass on a high fat diet is similar to controls

abnormal body fat mass ( J:158035 )

• do not develop increased adiposity on a high fat diet

decreased body weight ( J:247895 )

• at 4-4.5 and 8-8.5 months of age

• however, mice exhibit normal bone mineral density, bone mineral content, bone area, ratio of soft tissue attenuation, and percent adiposity

liver/biliary system

decreased liver tumor incidence ( J:143870 )

• fewer liver tumors after injection with Lewis lung carcinoma cells

hepatic steatosis ( J:158035 )

• resistant to hepatosteatosis

cellular

abnormal neuron differentiation ( J:129957 )

• reduced differentiation of progenitor cells into neurons

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki
Genetic Background	C.129P2-Tlr2^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)

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

immune system

immune system phenotype ( J:178054 )

N	• mice treated with peptidoglycan or muramyl dipeptide (MDP) develop arthritis with the same severity and incidence as in similarly treated wild-type mice

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)

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

immune system

increased B cell apoptosis ( J:135830 )

abnormal leukocyte migration ( J:171379 )

• Pam3Cys-treated mice exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

abnormal macrophage physiology ( J:70578 , J:103464 , J:130138 )

• macrophages are unresponsive to macrophage activating lipopeptide 2 kD (MALP-2) and tripalitoyl cysteinyl lipopeptide (Pam₃CSK₄) (J:70578)

• response of macrophages to synthetic analogs of B. burgdorferi and T. pallidum lipopeptides is completely abrogated (J:70578)

• normal response of macrophages to lipopeptides of other bacterial origins (J:70578)

• activation by peptidoglycan, zymosan, and propionibacterium acnes fails (J:103464)

• reduced production of TNF alpha in response to Porphyromonas gingivalis (J:130138)

abnormal osteoclast physiology ( J:130138 )

• cultural supernatant from P gingivalis stimulated peritoneal macrophage fails to stimulate osteoclast formation

decreased circulating interleukin-1 beta level ( J:119941 )

• reduced after both 30 and 60 minutes of reperfusion following ventricular ischemia

decreased circulating tumor necrosis factor level ( J:119941 )

• reduced after 30 but not 60 minutes of reperfusion following ventricular ischemia

abnormal cytokine secretion ( J:70578 )

• cytokine production by macrophages in response to both diacylated (macrophage activating lipopeptide 2 kD [MALP-2]) and triacylated lipopeptides (tripalitoyl cysteinyl lipopeptide [Pam₃CSK₄]), and synthetic analogs of B. burgdorferi and T. pallidum lipopeptides) is completely abrogated

decreased interleukin-12 secretion ( J:70578 )

• macrophages produce no NO and IL-12 in response to MALP-2 together with IFN-gamma or to Pam₃CSK₄

decreased interleukin-6 secretion ( J:70578 )

• MEFs treated with MALP-2 or Pam₃CSK₄ fail to produce IL-6

decreased tumor necrosis factor secretion ( J:70578 , J:103395 )

• macrophages produce no TNF-alpha in response to MALP-2 or Pam₃CSK₄ (J:70578)

• macrophages show impaired TNF-alpha production in response to heat-killed mycoplasma (J:70578)

• macrophages show no TNF-alpha production in response to the native mycobacterial 19-kDa lipoprotein and a synthetic triacylated lipopeptide, but respond normally to diacylated lipoprotein (J:103395)

decreased inflammatory response ( J:146111 )

• leukocyte influx into cerebrospinal fluid occurs but is less than in controls after S. pneumoniae injection into the spinal canal

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:146111 )

• no deaths during the experimental period from meningitis induced by Streptococcus pneumoniae

muscle

muscle phenotype ( J:116310 )

N	• MCP-1 (monocyte chemoattractant protein-1) release from isolated mouse aorta smooth muscle cells (MAoSMC) by stimulation with dsRNA is normal relative to controls

homeostasis/metabolism

abnormal response to cardiac infarction ( J:119941 )

• recovery of post-ischemic left ventricular contractile performance is greater than controls

decreased circulating interleukin-1 beta level ( J:119941 )

• reduced after both 30 and 60 minutes of reperfusion following ventricular ischemia

decreased circulating tumor necrosis factor level ( J:119941 )

• reduced after 30 but not 60 minutes of reperfusion following ventricular ischemia

decreased circulating alanine transaminase level ( J:135830 )

decreased cerebral infarct size ( J:128966 )

• relative infarction size is significantly smaller than in controls 72 hours after middle cerebral artery occlusion

liver/biliary system

abnormal hepatocyte morphology ( J:135830 )

• confluent foci of feathery hepatocyte degeneration due to bile acid cytotoxicity are significantly reduced compared to controls 24 hours after BDL

cardiovascular system

abnormal response to cardiac infarction ( J:119941 )

• recovery of post-ischemic left ventricular contractile performance is greater than controls

nervous system

decreased cerebral infarct size ( J:128966 )

• relative infarction size is significantly smaller than in controls 72 hours after middle cerebral artery occlusion

skeleton

abnormal osteoclast physiology ( J:130138 )

• cultural supernatant from P gingivalis stimulated peritoneal macrophage fails to stimulate osteoclast formation

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality ( J:146111 )

• no deaths during the experimental period from meningitis induced by Streptococcus pneumoniae

cellular

increased B cell apoptosis ( J:135830 )

abnormal leukocyte migration ( J:171379 )

• Pam3Cys-treated mice exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

hematopoietic system

increased B cell apoptosis ( J:135830 )

abnormal leukocyte migration ( J:171379 )

• Pam3Cys-treated mice exhibit reduced Ly6C^hi monocyte emigration from the bone marrow compared with similarly treated wild-type mice

abnormal macrophage physiology ( J:70578 , J:103464 , J:130138 )

• macrophages are unresponsive to macrophage activating lipopeptide 2 kD (MALP-2) and tripalitoyl cysteinyl lipopeptide (Pam₃CSK₄) (J:70578)

• response of macrophages to synthetic analogs of B. burgdorferi and T. pallidum lipopeptides is completely abrogated (J:70578)

• normal response of macrophages to lipopeptides of other bacterial origins (J:70578)

• activation by peptidoglycan, zymosan, and propionibacterium acnes fails (J:103464)

• reduced production of TNF alpha in response to Porphyromonas gingivalis (J:130138)

abnormal osteoclast physiology ( J:130138 )

• cultural supernatant from P gingivalis stimulated peritoneal macrophage fails to stimulate osteoclast formation

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

mortality/aging

decreased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:88174 )

• following i.p. injection with HSV-1 (KOS strain), homozygotes display delayed death and an overall reduction in mortality relative to wild-type controls: 5 of 8 homozygotes survive a challenge with 1-2 10⁹ pfu relative to only 2 of 8 wild-type controls

• following i.p. injection of 4-day-old mice with 10⁴ pfu of HSV-1, >60% of neonatal homozygotes survive the challenge, unlike wild-type and Tlr4^tm1Aki neonates which display a >90% lethality on day 6 postinfection

immune system

immune system phenotype ( J:76115 )

• homozygotes display normal lymphocyte composition relative to wild-type controls

• following an i.p. injection with E. coli O55:B5-derived LPS (1.0 mg), most homozygotes succumb to LPS shock 1-5 days after challenge, with only one-fifth of mice surviving on day 6, similar to wild-type controls

• in culture, mutant B cells display a normal dose-dependent mitogenic response and normal augmentation of MHC class II expression in response to S. minnesota (Re-595) LPS relative to wild-type B cells

decreased immunoglobulin level ( J:95726 )

• lower antibody titers are seen in response to immunization with lipidated OspA (Lyme disease vaccine) alone however titers are similar to wild-type when immunized with OspA plus complete Freund's adjuvant

abnormal macrophage physiology ( J:76115 , J:95726 )

• mutant peritoneal macrophages show impaired TNF production in response to cell wall preparations from several Gram-positive bacteria, including S. aureus, Corynebacterium diphtheriae, and Nocardia coeliaca (J:76115)

• mutant peritoneal macrophages display a severely impaired induction of NO₂^- in response to S. aureus peptidoglycan plus IFN-gamma (J:76115)

• however, when cultured with 1 ng/ml of Salmonella minnesota (Re-595) LPS or synthetic E. coli-type lipid A in the presence or absence of IFN-gamma, mutant thioglycollate-elicited peritoneal macrophages exhibit normal production of IL-6 and TNF relative to wild-type controls, with no difference in the amount of NO₂^- produced in the presence of IFN-gamma (J:76115)

• in addition, mutant peritoneal macrophages display normal production of TNF, IL-6 and NO₂^- in response to purified S. aureus lipoteichoic acid (J:76115)

• Il-6 and IL-10 production after stimulation with OspA or peptoglycan are reduced compared to wild-type (J:95726)

decreased microglial cell activation ( J:122551 )

• activation is significantly reduced after ischemia/reperfusion as measured by CD11b and GFAP induction

abnormal chemokine level ( J:88174 )

• unlike wild-type, mutant peritoneal macrophages fail to exhibit secretion of monocyte chemoattractant protein-1 (MCP-1) chemokine in response to HSV-1 challenge

• homozygotes produce significantly lower levels of brain MCP-1 than wild-type controls on day 1 postinfection with 10⁹ pfu HSV-1 KOS (a dose that is 50% lethal on day 4 in wild-type but not in mutant mice)

abnormal tumor necrosis factor level ( J:124334 )

• macrophage respond to both primary and secondary necrotic cells with reduced TNF alpha production

decreased interleukin-6 secretion ( J:76115 , J:88174 )

• mutant peritoneal macrophages fail to produce any detectable IL-6 levels in response to S. aureus peptidoglycan (J:76115)

• mutant peritoneal macrophages produce severely reduced IL-6 levels in response to challenge with herpes simplex virus 1 (HSV-1, KOS strain) (J:88174)

• mutant macrophages also fail to respond to zymosan (a TLR2 ligand), but do secrete IL-6 when challenged with LPS (a TLR4 ligand) (J:88174)

• following i.p. injection with 2 10⁹ pfu of HSV-1 (KOS strain), homozygotes display significantly lower serum IL-6 levels than wild-type controls on day 1 postinfection (J:88174)

decreased tumor necrosis factor secretion ( J:76115 )

• in culture, mutant peritoneal macrophages fail to produce any detectable TNF levels in response to cell wall preparations from S. aureus, even at high cell wall concentrations

• mutant peritoneal macrophages show impaired TNF production in response to cell wall preparations from other Gram-positive bacteria, including Corynebacterium diphtheriae, and Nocardia coeliaca

• mutant peritoneal macrophages display a severe defect in TNF production in response to S. aureus peptidoglycan

• however, mutant peritoneal macrophages display normal production of TNF in response to purified S. aureus lipoteichoic acid

• also, mutant peritoneal macrophages show a comparable dose-dependent production of TNF in response to increasing concentrations of S.minnesota LPS, relative to wild-type macrophages

increased susceptibility to bacterial infection ( J:95726 )

• the spirochete burden is significantly increased 2 weeks after infection with Borrelia burgdorferi, however antibody production, degree of arthritis and carditis, and time to disease resolution are the same as in wild-type mice

decreased susceptibility to Herpesvirales infection ( J:88174 )

• following i.p. injection with herpes simplex virus 1 (HSV-1, KOS strain), only 3 of 8 homozygotes display mild symptoms excluding total paralysis or seizures, relative to 6 of 8 wild-type controls and 6 of 8 Tlr4^tm1Aki homozygotes showing partial or total paralysis and/or seizures

• following i.p. injection of 4-day-old mice with 10⁴ pfu of HSV-1, at least 50% of neonatal homozygotes remain symptom-free for the entire 2-week observation period while 12% show only mild, transient symptoms, unlike wild-type and Tlr4^tm1Aki neonates which display a rapid onset of paralysis and death on day 6 postinfection

• following i.p. injection with 10⁹ pfu HSV-1 KOS, homozygotes display lower levels of brain MCP-1 on day 1 postinfection and significantly less brain inflammatory lesions with no hemorrhage on day 4 after challenge, relative to wild-type and Tlr4^tm1Aki mice

decreased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:88174 )

homeostasis/metabolism

abnormal response to cardiac infarction ( J:103019 )

• infarct size after ischemia/reperfusion is similar to controls

• left ventricular end diastole and end systole dimensions are less than for controls after ischemia/reperfusion injury

• increased fractional shortening after ischemia/reperfusion injury

abnormal glucose homeostasis ( J:124334 )

• resistant to STZ induced diabetes

abnormal chemokine level ( J:88174 )

• unlike wild-type, mutant peritoneal macrophages fail to exhibit secretion of monocyte chemoattractant protein-1 (MCP-1) chemokine in response to HSV-1 challenge

abnormal tumor necrosis factor level ( J:124334 )

• macrophage respond to both primary and secondary necrotic cells with reduced TNF alpha production

behavior/neurological

hyperresponsive to tactile stimuli ( J:122551 )

• after L5 spinal nerve transection, pain withdrawal threshold is reduced to 0.5 g from the normal 1g whereas control threshold drops to 0.05g measured at 7 days

abnormal locomotor behavior ( J:122597 )

• locomotor recovery impaired as measured 4-6 weeks after spinal cord injury

decreased thermal nociceptive threshold ( J:122551 )

• after L5 spinal nerve transection, thermal threshold withdrawal latency is reduced to 3 seconds from 4.5 seconds while control latency is reduced to 2 seconds measured at 7 days

nervous system

nervous system phenotype ( J:99051 )

N	• microglia induced with LPS undergo apoptosis just as do controls

abnormal glial cell physiology ( J:122551 )

• almost complete suppression of cytokine induction by supernatant from damaged sensory neurons in spinal cord glial cells

decreased microglial cell activation ( J:122551 )

• activation is significantly reduced after ischemia/reperfusion as measured by CD11b and GFAP induction

abnormal astrocyte physiology ( J:122551 )

• activation is significantly reduced after ischemia/reperfusion as measured by CD11b and GFAP induction

cardiovascular system

abnormal heart morphology ( J:103019 )

decreased heart weight ( J:103019 )

• lower than controls before and after myocardial infarction

abnormal heart ventricle morphology ( J:103019 )

• less ventricular dilation than controls after ischemia/reperfusion

decreased heart left ventricle weight ( J:103019 )

• lower than controls before and after myocardial infarction

cardiac interstitial fibrosis ( J:103019 )

• less myocardial fibrosis in non-infarcted interstitial areas than for controls

abnormal response to cardiac infarction ( J:103019 )

• infarct size after ischemia/reperfusion is similar to controls

• left ventricular end diastole and end systole dimensions are less than for controls after ischemia/reperfusion injury

• increased fractional shortening after ischemia/reperfusion injury

respiratory system

decreased lung weight ( J:103019 )

• lower than controls before and after myocardial infarction

hematopoietic system

decreased immunoglobulin level ( J:95726 )

abnormal macrophage physiology ( J:76115 , J:95726 )

• mutant peritoneal macrophages display a severely impaired induction of NO₂^- in response to S. aureus peptidoglycan plus IFN-gamma (J:76115)

• in addition, mutant peritoneal macrophages display normal production of TNF, IL-6 and NO₂^- in response to purified S. aureus lipoteichoic acid (J:76115)

• Il-6 and IL-10 production after stimulation with OspA or peptoglycan are reduced compared to wild-type (J:95726)

decreased microglial cell activation ( J:122551 )

• activation is significantly reduced after ischemia/reperfusion as measured by CD11b and GFAP induction

cellular

cardiac interstitial fibrosis ( J:103019 )

• less myocardial fibrosis in non-infarcted interstitial areas than for controls

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki
Genetic Background	NOD.129P2-Tlr2^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:124334 )

• significantly reduced susceptibility to type 1 diabetes

• 38% are diabetic at 45 weeks as compared to 74% of controls

endocrine/exocrine glands

insulitis ( J:124334 )

• reduced insulitis relative to controls

immune system

insulitis ( J:124334 )

• reduced insulitis relative to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	type 1 diabetes mellitus	DOID:9744	OMIM:222100	J:124334

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr4^tm1Aki/Tlr4^tm1Aki
Genetic Background	B6.129P2-Tlr2^tm1Aki Tlr4^tm1Aki

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)
Tlr4^tm1Aki mutation (7 available); any Tlr4 mutation (91 available)

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

cellular

increased apoptosis ( J:102879 )

• 5 days after lung injury, mutants show significantly increased numbers of apoptotic lung epithelial and inflammatory cells

homeostasis/metabolism

hyperoxia ( J:102879 )

• mutant mice are more sensitive to hyperoxia; survival time of mutants after hyperoxia exposure is reduced by almost 50% compared to wild-type

increased physiological sensitivity to xenobiotic ( J:102879 )

• double knockout mice are more susceptible to bleomycin-induced lung injury

immune system

abnormal chemokine secretion ( J:102879 )

• hyaluronan fragment-induced expression of chemokines by peritoneal macrophages is completely abolished in double knockout mice

• 5 days after lung injury, mutant mice produce significantly lower amounts of chemotactic factor KC in the alveolar space

respiratory system

abnormal lung interstitium morphology ( J:102879 )

• lung tissue from mutant mice shows evidence of enhanced injury with thickened interstitium and increased inflammatory cell accumulation within the interstitium

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr4^tm1Aki/Tlr4^tm1Aki
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

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

immune system

decreased IgG3 level ( J:117688 )

• significantly reduced in serum at 7 and 11 weeks of age

abnormal macrophage physiology ( J:117688 )

• in response to purified LPS, a Tlr4 agonist, or a Tlr2 agonist, macrophages do not produced TNFalpha or Il10, while production after stimulation by CpG, a Tlr9 agonist

• production of these cytokines is reduced upon stimulation with heat-killed gram negative bacteria, whereas response to gram-positive bacteria is comparable to wild-type

abnormal cytokine secretion ( J:117688 )

• TNFalpha and Il10 production is absent in response to Tlr2 or Tlr4 agonists, and is reduced in response to heat-killed gram negative bacteria

hematopoietic system

decreased IgG3 level ( J:117688 )

• significantly reduced in serum at 7 and 11 weeks of age

abnormal macrophage physiology ( J:117688 )

• in response to purified LPS, a Tlr4 agonist, or a Tlr2 agonist, macrophages do not produced TNFalpha or Il10, while production after stimulation by CpG, a Tlr9 agonist

• production of these cytokines is reduced upon stimulation with heat-killed gram negative bacteria, whereas response to gram-positive bacteria is comparable to wild-type

Allelic Composition	Tlr2^tm1Aki/Tlr2^tm1Aki Tlr6^tm1Aki/Tlr6^tm1Aki
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr2^tm1Aki mutation (7 available); any Tlr2 mutation (60 available)
Tlr6^tm1Aki mutation (1 available); any Tlr6 mutation (50 available)

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

immune system

decreased interleukin-6 secretion ( J:70578 )

• MEFs treated with diacylated (macrophage activating lipopeptide 2 kD [MALP-2]) and triacylated lipopeptides (tripalitoyl cysteinyl lipopeptide [Pam₃CSK₄]) fail to produce IL-6

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 11/19/2024 MGI 6.24