Phenotypes Associated with This Genotype

Genotype
MGI:3665469

• Allelic Composition: Tlr4^tm1Aki/Tlr4^tm1Aki
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

immune system

decreased B cell proliferation ( J:76115 )

• unlike wild-type splenocytes, mutant B cells fail to exhibit a proliferative response to various concentrations of S. minnesota LPS

abnormal macrophage physiology ( J:76115 )

• in culture, mutant thioglycollate-elicited peritoneal macrophages fail to produce any detectable levels of IL-6 and TNF in response to 1 ng/ml of Salmonella minnesota (Re-595) LPS or synthetic E. coli-type lipid A, even in the presence of IFN-gamma

• mutant thioglycollate-elicited peritoneal macrophages fail to produce any NO₂^- in response to S. minnesota LPS or lipid A, even in the presence of IFN-gamma

• unlike wild-type, mutant peritoneal macrophages fail to secrete TNF in response to increasing concentrations of S. minnesota LPS

• mutant peritoneal macrophages show severely impaired production of TNF, IL-6 and NO₂^- in response to S. aureus lipoteichoic acid

• however, mutant peritoneal macrophages display normal production of NO₂^- in response to S. aureus peptidoglycan plus IFN-gamma

abnormal level of surface class II molecules ( J:76115 )

• unlike wild-type splenocytes, mutant B cells fail to exhibit augmentation of MHC class II expression in response to S. minnesota LPS

• in contrast, augmentation of MHC class II expression in response to IL-4 is normal, indicating that this defect is LPS-specific

decreased interleukin-6 secretion ( J:76115 )

• mutant thioglycollate-elicited peritoneal macrophages fail to produce any detectable levels of IL-6 in response to 1 ng/ml of Salmonella minnesota (Re-595) LPS or synthetic E. coli-type lipid A, even in the presence of IFN-gamma

• mutant peritoneal macrophages show severely impaired production of IL-6 in response to S. aureus lipoteichoic acid

• in contrast, mutant peritoneal macrophages produce comparable amounts of IL-6 in response to S. aureus peptidoglycan

decreased tumor necrosis factor secretion ( J:76115 )

• mutant thioglycollate-elicited peritoneal macrophages fail to produce any detectable levels of TNF in response to 1 ng/ml of Salmonella minnesota (Re-595) LPS or synthetic E. coli-type lipid A, even in the presence of IFN-gamma

• unlike wild-type, mutant peritoneal macrophages fail to secrete TNF in response to various concentrations of S. minnesota LPS

• mutant peritoneal macrophages show a significant reduction in TNF secretion in response to cell wall preparations from S. aureus; however, TNF production in response to C. diphtheria and N. coeliaca cell walls is not severely affected

• mutant, but not wild-type, peritoneal macrophages display a severely impaired production of TNF in response to S. aureus and S. sanguis lipoteichoic acid

• however, mutant peritoneal macrophages show a normal, dose-dependent increase in TNF levels in response to S. aureus peptidoglycan

decreased susceptibility to endotoxin shock ( J:76115 )

• following an i.p. injection with E. coli O55:B5-derived LPS (1.0 mg), all homozygotes remain alive on day 6, whereas most wild-type controls succumb to shock 1-5 days after challenge, with only one-fifth surviving on day 6

increased susceptibility to bacterial infection ( J:111778 )

• when infected i.p. with S. typhimurium, Tlr4 mutants show increased susceptibility (100% mortality by 4 days) compared to wild-type or Tlr5 mutants (100% mortality by 5 days)

• at dose of 6 x 10⁶ cfu, mutants succumb to infection by 2 days, similar to wild-type and Tlr5 mutants

hematopoietic system

decreased B cell proliferation ( J:76115 )

• unlike wild-type splenocytes, mutant B cells fail to exhibit a proliferative response to various concentrations of S. minnesota LPS

abnormal macrophage physiology ( J:76115 )

• in culture, mutant thioglycollate-elicited peritoneal macrophages fail to produce any detectable levels of IL-6 and TNF in response to 1 ng/ml of Salmonella minnesota (Re-595) LPS or synthetic E. coli-type lipid A, even in the presence of IFN-gamma

• mutant thioglycollate-elicited peritoneal macrophages fail to produce any NO₂^- in response to S. minnesota LPS or lipid A, even in the presence of IFN-gamma

• unlike wild-type, mutant peritoneal macrophages fail to secrete TNF in response to increasing concentrations of S. minnesota LPS

• mutant peritoneal macrophages show severely impaired production of TNF, IL-6 and NO₂^- in response to S. aureus lipoteichoic acid

• however, mutant peritoneal macrophages display normal production of NO₂^- in response to S. aureus peptidoglycan plus IFN-gamma

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:162097 )

• skin cancers induced using croton oil and 7,12-dimethylbenz(a)anthracene

• reduced number of papillomas and carcinomas relative to controls

• growth of established tumors not affected in tumor transplant studies

neoplasm

decreased incidence of tumors by chemical induction ( J:162097 )

• skin cancers induced using croton oil and 7,12-dimethylbenz(a)anthracene

• reduced number of papillomas and carcinomas relative to controls

• growth of established tumors not affected in tumor transplant studies

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:168789 )

N • cisplatin and lipopolysaccharide treatment does not lead to significant increases in auditory brainstem response as is observed in controls

cellular

decreased B cell proliferation ( J:76115 )

• unlike wild-type splenocytes, mutant B cells fail to exhibit a proliferative response to various concentrations of S. minnesota LPS