Phenotypic and functional characterization of mice that lack the type I receptor for IL-1.
IL-1 alpha and IL-1 beta bind to receptors termed the type I and type II IL-1 receptors. The type I IL-1 receptor is responsible for specific signaling, while the type II IL-1 receptor functions as a nonsignaling decoy receptor. To determine the effect of a defect in IL-1-mediated signaling, mice have been produced with a genetically disrupted type I IL-1 receptor gene. Mice lacking type I IL-1 receptors are of normal vigor and exhibit no overt phenotype. B cells from type I IL-1R-/- mice activated in vitro with anti-IgM do not proliferate in response to IL-1, but do so in response to IL-4. Injection of murine IL-1 alpha does not induce detectable serum IL-6 levels in type I IL-1R-/- mice, but equivalent levels are produced in response to LPS. Type I IL-1R-/- mice have normal serum Ig levels and generate equivalent primary and secondary Ab responses as wild-type mice. In response to LPS, acute phase protein mRNA induction are equivalent in type I IL-1R-/- and wild-type mice. Type I IL-1R-/- mice do not differ from control mice in susceptibility to either a lethal challenge with D-galactosamine plus LPS or high dose LPS. Interestingly, ICE-/-/type I IL-1R-/- double mutant mice are resistant to high dose LPS. Type I IL-1R-/- mice backcrossed to the C57BL/6 background were as equally resistant as wild-type mice to Listeria monocytogenes.
Glaccum
M B
MB
Immunex Corporation, Seattle, WA 98101, USA.
Stocking
K L
KL
Charrier
K
K
Smith
J L
JL
Willis
C R
CR
Maliszewski
C
C
Livingston
D J
DJ
Peschon
J J
JJ
Morrissey
P J
PJ
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000818:Animals; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008088:Listeriosis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics* / Q000276:immunology*; D010641:Phenotype; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D003546:Cysteine Endopeptidases; D020170:Caspase 1