• IL6 is a cytokine that functions in inflammation and the maturation of B cells. IL6 is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of IL6 is implicated in a wide variety of inflammation-associated disease states, such as rheumatoid arthritis.
• The exons 1-5 of mouse Il6 gene that encode whole protein is replaced by human counterparts in B-hIL6/hIL6R mice(C). The promoter, 5’UTR and 3’UTR region of the mouse Il6 are also replaced by human counterparts. The CDS of human IL6R gene was inserted after the start codon ATG of mouse Il6ra gene in B-hIL6/hIL6R mice(C).
• Mouse IL6 was exclusively detectable in the wild-type BALB/cCrSlcNifdc mice after LPS stimulation. Human IL6 was exclusively detectable in the homozygousB-hIL6/hIL6R mice(C) after LPS stimulation, but not in wild-type mice.
• Soluble human IL6R was exclusively detectable in homozygous B-hIL6/hIL6R mice(C).
• Mouse IL6R protein was only detectable in wild-type BALB/cCrSlcNifdc mice, and human IL6R protein was exclusively detectable in homozygous B-hIL6/hIL6R mice(C).
• This product is used for the evaluation of the pharmacodynamics and safety of anti-human IL6/IL6R antibodies in autoimmune diseases.

Gene targeting strategy for B-hIL6/hIL6R mice(C). 

The exons 1-5 of mouse Il6 gene that encode whole protein is replaced by human counterparts in B-hIL6/hIL6R mice(C). The promoter, 5’UTR and 3’UTR region of the mouse Il6 are also replaced by human counterparts.

The CDS of human IL6R gene was inserted after the start codon ATG of mouse Il6ra gene in B-hIL6/hIL6R mice(C).

Strain specific IL6R expression analysis in wild-type BALB/cCrSlcNifdc mice and homozygous B-hIL6/IL6R mice(C) by flow cytometry. Splenocytes were collected from wild-type BALB/cCrSlcNifdc mice and homozygous B-hIL6/IL6R mice(C), and analyzed by flow cytometry with species-specific anti-mIL-6Rα Antibody (PE anti-mouse CD126 (IL-6Rα chain) Antibody, biolegend, 115805) and anti-hIL-6Rα Antibody (PE anti-human CD126 (IL-6Rα) Antibody, biolegend, 352803). Mouse IL6R was detectable in T cells of wild-type mice. Human IL6R was detectable in T cells of homozygous B-hIL6/IL6R mice(C).

Strain specific soluble IL6R expression analysis in wild-type BALB/cCrSlcNifdc mice and homozygous B-hIL6/IL6R mice(C) by ELISA. Serum was collected from wild-type BALB/cCrSlcNifdc mice (female, n=3), homozygous B-hIL6/IL6R mice(C) (female, n=3). Expression level of soluble human IL6R were analyzed by ELISA (Human IL6R ELISA Kit (DR600)). Human IL6R was detectable in homozygous B-hIL6/IL6R mice(C). Values are expressed as mean ± SEM.

Strain specific IL6 expression analysis in wild-type BALB/cCrSlcNifdc mice and homozygous B-hIL6/IL6R mice(C) by ELISA. Serum was collected from wild-type BALB/cCrSlcNifdc mice (female, n=3), homozygous B-hIL6/IL6R mice(C) (female, n=3), the production of IL6 in serum were assessed after 3 h of stimulation with LPS (20 μg/200uL, i.p.) in vivo. Expression level of mouse and human IL6 were analyzed by ELISA (ELISA MAX™ Deluxe Set Mouse IL-6(431304); ELISA MAX™ Deluxe Set Human IL-6 (430508)). Mouse IL6 was only detectable in wild-type BALB/cCrSlcNifdc mice. Human IL6 was only detectable in homozygous B-hIL6/IL6R mice(C). Values are expressed as mean ± SEM.