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Phenotypes Associated with This Genotype
Genotype
MGI:3665468
Allelic
Composition
Tlr5tm1Flv/Tlr5tm1Flv
Genetic
Background
involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tlr5tm1Flv mutation (2 available); any Tlr5 mutation (56 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• 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
• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation
• 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
• 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
• 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
• 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
• 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
• 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
• significantly higher serum cholesterol levels
• significantly higher serum triglyceride levels
• serum lipocalin-2 levels are elevated
• 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
• basal serum insulin levels are significantly higher than normal, with an average over .55 nm/mL
• 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
• 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
• magnetic resonance imaging shows increased fat mass throughout the body, especially the visceral fat
• at 20 weeks of age the epididymal fat pads are approximately 2 fold greater than normal
• adipose tissue has a higher than normal production of interferon gamma and interleukin 1 beta

growth/size/body
• 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
• 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
• 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
• 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
• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation

cardiovascular system
• average is raised to approximately 110mm Hg
• average is increased to appoximately 130mm Hg

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

endocrine/exocrine glands
• 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
• 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
• 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


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)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory