immune system
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• 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
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• 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
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• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation
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• 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
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• 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
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• 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
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• 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
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• 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
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homeostasis/metabolism
adipose tissue
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• magnetic resonance imaging shows increased fat mass throughout the body, especially the visceral fat
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• at 20 weeks of age the epididymal fat pads are approximately 2 fold greater than normal
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• adipose tissue has a higher than normal production of interferon gamma and interleukin 1 beta
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growth/size/body
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• 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
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• 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
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digestive/alimentary system
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• 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
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• 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
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hematopoietic system
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• neutrophils are absent from BALFs from challenged mutants but wild-type show significant accumulation
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cardiovascular system
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• average is raised to approximately 110mm Hg
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• average is increased to appoximately 130mm Hg
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behavior/neurological
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• homozygotes consume approximately 10% more food than wild-type controls and have greater stool output
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endocrine/exocrine glands
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• 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
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liver/biliary system
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• 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
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respiratory system
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• 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
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