Basic Information
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Targeting strategy
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Gene targeting strategy for B-hIL11RA mice.
The exons 2-11 of mouse Il11ra1 gene that encode the extracellular domain were replaced by human IL11RA exons 2-11 in B-hIL11RA mice.
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mRNA expression analysis
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Species-specific IL11RA gene expression analysis in wild-type and humanized B-hIL11RA mice by RT-PCR. Murine Il11ra1 mRNA was detected in liver cells isolated from wild-type (+/+) mice, while human IL11RA mRNA was exclusively detected in homozygous B-hIL11RA (H/H) mice.
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Protein expression analysis
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Species-specific IL11RA protein expression analysis in humanized B-hIL11RA mice. Tissue was extracted from wild-type C57BL/6 (+/+) and homozygous B-hIL11RA (H/H) mice and analyzed by western blot using species-specific anti-IL11RA antibodies. Murine IL11RA1 and human IL11RA proteins were detected in liver tissue isolated from wild-type mice and B-hIL11RA mice, due to the cross-reactivity of the antibody.
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In vivo efficacy of anti-human IL11RA antibody with APAP-induced liver damage in B-hIL11RA mice
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Reduction in APAP-induced liver damage with anti-IL11RA in male B-hIL11RA mice.(A) Schematic showing therapeutic dosing of APAP-injured mice. B-hIL11RA mice (male, 8 weeks, n=5) treated with PBS/anti-hIL11RA (in house, 15 mg/kg) were fasted overnight and inducted with APAP(400 mg/kg) for 24 h. Blood and liver tissue were collected for analysis. (B) Serum levels of ALT and AST were reduced in the anti-hIL11RA antibody-treated male mice group compared to the control. Values are expressed as mean ± SD. *p<0.05.
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In vivo efficacy of anti-human IL11RA antibody with APAP-induced liver damage in B-hIL11RA mice
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Reduction in APAP-induced liver damage with anti-IL11RA in male B-hIL11RA mice.(A) Representative H&E-stained liver images (representative dataset from n = 5 per group). (B) Statistical analysis of necrosis area(% of total area). Values are expressed as mean ± SD. *p<0.05.
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In vivo efficacy of anti-human IL11RA antibody with APAP-induced liver damage in B-hIL11RA mice
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Reduction in APAP-induced liver damage with anti-IL11RA in male B-hIL11RA mice.(A) Representative TUNEL-stained liver images (representative dataset from n=5 per group). (B) Statistical analysis of TUNEL positive cells(% of total cells). Values are expressed as mean ± SD. *p<0.05.
