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
hypertension
(
J:158055
)
• average is raised to approximately 110mm Hg
|
• average is increased to appoximately 130mm Hg
|
behavior/neurological
polyphagia
(
J:158055
)
• 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
|