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 (56 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

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

hepatic steatosis ( J:158035 )

• resistant to hepatosteatosis

decreased liver tumor incidence ( J:143870 )

• fewer liver tumors after injection with Lewis lung carcinoma cells

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 (56 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 (56 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 (56 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 (56 available)
Tlr4^tm1Aki mutation (7 available); any Tlr4 mutation (90 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 (56 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

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