Gene targeting strategy for B-hIL11RA mice. The exons 3-11 of mouse Il11ra1 gene that encode the extracellular domain were replaced by human IL11RA exons 3-11 in B-hIL11RA mice.

Strain specific analysis of IL11RA gene expression in wild-type mice and B-hIL11RA mice by RT-PCR. Mouse Il11ra1 mRNA was detectable in liver of wild-type mice (+/+). Human IL11RA mRNA was detectable only in homozygous B-hIL11RA mice but not in wild-type mice.

Strain specific IL11RA expression analysis in homozygous B-hIL11RA mice by western blot. Tissue was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hIL11RA mice (H/H), and analyzed by western blot with anti-IL11RA antibody. Mouse IL11RA1 and human IL11RA were detectable in wild type mice and homozygous B-hIL11RA mice, as the antibody is crossly reactive with IL11RA in human and mice. Mice IL11RA1 and human IL11RA were not detectable in kidney, which might be because of low protein levels compared with liver.

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

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.

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.