Phenotypes associated with this allele

• Allele Symbol: Tlr5^tm1Flv
• Allele Name: targeted mutation 1, Richard Flavell
• Allele ID: MGI:3665162
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlr5^tm1Flv/Tlr5^tm1Flv	involves: 129S1/Sv	MGI:4950287
hm2	Tlr5^tm1Flv/Tlr5^tm1Flv	involves: 129S1/Sv * C57BL/6	MGI:3665468
cx3	Tlr4^tm1Aki/Tlr4^tm1Aki Tlr5^tm1Flv/Tlr5^tm1Flv	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3665470

Genotype
MGI:4950287

hm1

• Allelic Composition: Tlr5^tm1Flv/Tlr5^tm1Flv
• Genetic Background: involves: 129S1/Sv

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

immune system

abnormal leukocyte migration ( J:171379 )

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

cellular

abnormal leukocyte migration ( J:171379 )

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

hematopoietic system

abnormal leukocyte migration ( J:171379 )

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

Genotype
MGI:3665468

hm2

• Allelic Composition: Tlr5^tm1Flv/Tlr5^tm1Flv
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

increased susceptibility to induced colitis ( J:158055 )

• while 10% of homozygotes have severe colitis and and additional 30% have less severe colitis, the severity of colitis is greatly attenuated in homozygotes rederived into a cleaner environment

increased susceptibility to induced pancreatitis ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

decreased neutrophil cell number ( J:111778 )

• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation

abnormal dendritic cell physiology ( J:111778 )

• when mutants are injected i.p. with flagellin, splenic cells show no response after 6 hours, whereas cells from wild-type mice display maturation markers in response to flagellin

• mutant cells show normal responses to LPS injection

abnormal cytokine secretion ( J:111778 )

• after i.p. injection with flagellin, wild-type mice show elevated serum levels of Il-6 at 2 hours and Il-12 at 2 and 4 hours after challenge but mutants are unresponsive

• elevated Il-6 and Il-12 mRNA levels are detected in cultured wild-type dendritic cells in response to flagellin; mutant DCs show little response although response to LPS is similar to wild-type

• increases in Il-6 and keratinocyte chemoattractant in BALFs after challenge are present in wild-type but absent in mutants

increased susceptibility to autoimmune diabetes ( J:158055 )

lung inflammation ( J:111778 )

• after intranasal (i.n.) challenge with flagellin, at 10 and 24 hours after challenge bronchoalveolar lavage fluids (BALFs) from mutants show no cell infiltration while wild-type mice have elevated cell content and infiltration

increased susceptibility to bacterial infection ( J:111778 )

• when infected by i.p. with S. typhimurium (SB300) and a non-flagellated form (SB762) wild-type and mutants show similar survival time and bacterial load in spleens and livers

• infection with P. aeruginosa (1 x 10⁶ cfu) results in similar survival rates to wild-type at 7 weeks of age (~85-90%)

• at dose of 6 x 10⁶ cfu, mutants succumb to infection in 2 days

abnormal response to transplant ( J:111778 )

• when wild-type bone marrow is transplanted into Tlr5 mutants, significant amounts of Il-6 are found in sera upon flagellin challenge; when Tlr5 -null bone marrow is put into wild-type mice, flagellin challenge only results in a small Il-6 response

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

increased circulating cholesterol level ( J:158055 )

• significantly higher serum cholesterol levels

increased circulating triglyceride level ( J:158055 )

• significantly higher serum triglyceride levels

increased circulating lipocalin 2 level ( J:158055 )

• serum lipocalin-2 levels are elevated

abnormal glucose homeostasis ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

• after a 15 hour fast homozygotes on a normal diet have slightly elevated glucose levels and when non-fasting homozygotes are administered a bolus of glucose they display an impaired ability to restore blood glucose to baseline levels

increased circulating insulin level ( J:158055 )

• basal serum insulin levels are significantly higher than normal, with an average over .55 nm/mL

insulin resistance ( J:158055 )

• the amount of insulin produced in response to a glucose challenge is significantly increased to approximately 1.2 nm/mL, serum levels of lipocalin 2 are elevated, and the number and size of pancreatic islets that stain positive for insulin is increased

• although food restriction prevents increased body and fat pad mass, increased serum glucose, lipids, and insulin, food restricted homozygotes still have a decreased response to exogenous insulin

abnormal physiological response to xenobiotic ( J:158055 )

• decimation of the gut microbiota by treatment with broad spectrum antibiotics for 12 weeks beginning at wean age corrects the metabolic syndrome that develops in the absence of antibiotics

adipose tissue

increased total body fat amount ( J:158055 )

• magnetic resonance imaging shows increased fat mass throughout the body, especially the visceral fat

increased epididymal fat pad weight ( J:158055 )

• at 20 weeks of age the epididymal fat pads are approximately 2 fold greater than normal

abnormal adipose tissue physiology ( J:158055 )

• adipose tissue has a higher than normal production of interferon gamma and interleukin 1 beta

growth/size/body

increased body weight ( J:158055 )

obese ( J:158055 )

• by 4 weeks of age the body mass is an average of 15% above that of normal controls and in homozygotes rederived into a clean facility the body mass at 20 weeks of age is 20% greater than normal controls in both males and females

increased susceptibility to diet-induced obesity ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

digestive/alimentary system

abnormal gut flora balance ( J:158055 )

• the gut microbiotica shows enrichment or reduction of 116 bacterial phylotypes relative to wild-type controls and transplanting gut microbiota from homozygotes to germ-free control hosts confers many aspects of the metabolic disease phenotype

increased susceptibility to induced colitis ( J:158055 )

• while 10% of homozygotes have severe colitis and and additional 30% have less severe colitis, the severity of colitis is greatly attenuated in homozygotes rederived into a cleaner environment

hematopoietic system

decreased neutrophil cell number ( J:111778 )

• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation

cardiovascular system

increased systemic arterial blood pressure ( J:158055 )

hypertension ( J:158055 )

increased systemic arterial diastolic blood pressure ( J:158055 )

• average is raised to approximately 110mm Hg

increased systemic arterial systolic blood pressure ( J:158055 )

• average is increased to appoximately 130mm Hg

behavior/neurological

abnormal eating behavior ( J:158055 )

polyphagia ( J:158055 )

• homozygotes consume approximately 10% more food than wild-type controls and have greater stool output

endocrine/exocrine glands

increased susceptibility to induced pancreatitis ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

liver/biliary system

hepatic steatosis ( J:158055 )

• when homozygotes are fed a high-fat diet they develop inflammatory infiltrates in the pancreatic islets, have fasting glucose concentrations greater than 120 mg/dL, and display hepatic steatosis

respiratory system

lung inflammation ( J:111778 )

• after intranasal (i.n.) challenge with flagellin, at 10 and 24 hours after challenge bronchoalveolar lavage fluids (BALFs) from mutants show no cell infiltration while wild-type mice have elevated cell content and infiltration

Genotype
MGI:3665470

cx3

• Allelic Composition: Tlr4^tm1Aki/Tlr4^tm1Aki; Tlr5^tm1Flv/Tlr5^tm1Flv
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

immune system

increased susceptibility to bacterial infection ( J:111778 )

• double mutants are somewhat more susceptible to infection than either single mutant (100% mortality by 2.5 days)

• upon infection i.n. with P. aeruginosa (1 x 10⁶ cfu), double mutants show increased susceptibility (decreased survival to ~65%)

• at dose of 6 x 10⁶ cfu, mutants succumb to infection by 12 hours