Key Advantages
Validation
Application
In IL1RACP humanized mice (B-hIL1RACP), a chimeric CDS encoding the human IL1RAcP signal peptide and extracellular domain together with the mouse IL1RAcP transmembrane and cytoplasmic domains was inserted after the 5’ UTR of the mouse Il1racp gene. The chimeric IL1RAcP protein is driven by the endogenous mouse Il1racp promoter, while mouse Il1racp transcription and translation are disrupted.
Strain-specific analysis of mouse and human IL1RACP mRNA expression in wild-type C57BL/6 mice and IL1RACP humanized mice by RT-PCR. Liver tissues were collected from wild-type C57BL/6 mice (+/+) and homozygous IL1RACP humanized mice (H/H). cDNA was synthesized by reverse transcription, followed by PCR amplification using mouse- or human-specific IL1RACP primers. Mouse Il1racp mRNA was detected in wild-type C57BL/6 mice, whereas human IL1RACP mRNA was detected in homozygous IL1RACP humanized mice but not in wild-type mice.
Strain-specific analysis of human IL1RACP protein expression in wild-type C57BL/6 mice and IL1RACP humanized mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice and homozygous IL1RACP humanized mice (H/H). Human IL1RACP protein expression was analyzed by flow cytometry using an anti-human IL1RACP antibody (R&D Systems, FAB676P). Human IL1RACP was detected in homozygous IL1RACP humanized mice but not in wild-type C57BL/6 mice.
In vitro functional analysis of IL1, IL33, and IL36-induced cytokine responses in splenocytes from IL1RACP humanized mice. Splenocytes were collected from wild-type mice and homozygous IL1RACP humanized mice (H/H) and stimulated in vitro with IL1, IL33, or IL36 proteins. Cytokine levels in the splenocyte culture supernatants were measured after 48 hours. Mouse IL1, IL33, and IL36 proteins effectively activated wild-type splenocytes and induced cytokine secretion. Mouse IL1β and IL33 also activated splenocytes from IL1RACP humanized mice, whereas mouse IL36 did not effectively induce splenocyte activation.
Western blot analysis of IL1RAcP protein expression in various tissues of wild-type C57BL/6JNifdc mice and IL1RACP humanized mice. Heart, liver, spleen, lung, kidney, and brain tissues were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous IL1RACP humanized mice (H/H). IL1RAcP protein expression was analyzed by Western blot using an anti-IL-1RAP polyclonal antibody (Proteintech, 30966-1-AP), which cross-reacts with both human and mouse IL1RAcP proteins. IL1RAcP protein was detected in the heart, liver, spleen, lung, kidney, and brain of both wild-type C57BL/6JNifdc mice and homozygous IL1RACP humanized mice. WT: wild-type C57BL/6JNifdc mice; HO: homozygous IL1RACP humanized mice.
Western blot analysis of IL1RAcP protein expression in various tissues of wild-type C57BL/6JNifdc mice and IL1RACP humanized mice. Uterus, testis, skin, eyeball, stomach, large intestine, and small intestine tissues were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous IL1RACP humanized mice (H/H). IL1RAcP protein expression was analyzed by Western blot using an anti-IL-1RAP polyclonal antibody (Proteintech, 30966-1-AP), which cross-reacts with both human and mouse IL1RAcP proteins. IL1RAcP protein was detected in the uterus, testis, skin, eyeball, stomach, large intestine, and small intestine of both wild-type C57BL/6JNifdc mice and homozygous IL1RACP humanized mice. WT: wild-type C57BL/6JNifdc mice; HO: homozygous IL1RACP humanized mice.
Western blot analysis of IL1RAcP protein expression in various tissues of wild-type C57BL/6JNifdc mice and IL1RACP humanized mice. Trachea, esophagus, bladder, thymus, lymph node, ovary, and epididymis tissues were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous IL1RACP humanized mice (H/H). IL1RAcP protein expression was analyzed by Western blot using an anti-IL-1RAP polyclonal antibody (Proteintech, 30966-1-AP), which cross-reacts with both human and mouse IL1RAcP proteins. IL1RAcP protein was detected in the trachea, esophagus, bladder, thymus, lymph nodes, ovary, and epididymis of both wild-type C57BL/6JNifdc mice and homozygous IL1RACP humanized mice. WT: wild-type C57BL/6JNifdc mice; HO: homozygous IL1RACP humanized mice.
Macroscopic anatomical and histopathological analysis of major organs in wild-type C57BL/6 mice and IL1RACP humanized mice. Eight-week-old wild-type C57BL/6 mice and IL1RACP humanized mice (10 males and 10 females) were monitored for 8 weeks to assess overall health. (A) Organ weights of wild-type C57BL/6 mice and IL1RACP humanized mice. (B) Histopathological analysis of major organs by hematoxylin and eosin (H&E) staining. No abnormalities in organ morphology or histopathology were observed in IL1RACP humanized mice compared with wild-type controls.
Complete blood count (CBC) of IL1RACP humanized mice. Values are expressed as mean ± SD.
Values are expressed as mean ± SD.
Experimental schedule for an imiquimod (IMQ)-induced psoriasis model in IL1RACP humanized mice. IL1RACP humanized mice (7 weeks old) received daily topical applications of commercially available imiquimod (IMQ) cream to the shaved dorsal skin for 6 consecutive days to induce psoriasis-like skin inflammation. Control mice received topical applications of Vaseline cream following the same schedule. The severity of skin inflammation was assessed daily, and dorsal skin tissues were collected at the experimental endpoint. IMQ: imiquimod.
Evaluation of imiquimod (IMQ)-induced psoriasis-like skin inflammation and in vivo efficacy of a CAN10 analog in IL1RACP humanized mice. Female IL1RACP humanized mice (7 weeks old, n = 5) were treated with imiquimod (IMQ) cream to induce psoriasis-like skin inflammation. Body weight and clinical signs of skin inflammation were monitored daily for up to 7 days. Mice in each group received an in-house CAN10 analog at a dose of 10 mg/kg. (A) Experimental schedule for the induction of psoriasis-like skin lesions. (B) Representative images of dorsal skin lesions on day 6. (C) Body weight changes during treatment. (D–E) Erythema and scaling scores of dorsal skin, assessed daily. The cumulative severity score (erythema plus scaling) is also presented. Statistical significance was determined using two-way ANOVA. ***p < 0.001.
Histopathological evaluation of anti-IL1RAcP antibody efficacy in imiquimod (IMQ)-induced psoriasis-like skin lesions in IL1RACP humanized mice. Dorsal skin tissues were collected at the experimental endpoint and analyzed by hematoxylin and eosin (H&E) staining. (A) Representative H&E-stained sections of dorsal skin. (B) Histopathological scores of skin lesions. Treatment with an in-house CAN10 analog (10 mg/kg) significantly improved psoriasis-like skin histopathology, including reductions in hyperkeratosis, crusting, and acanthosis. These results demonstrate the utility of IL1RACP humanized mice as a preclinical model for evaluating the in vivo therapeutic efficacy of anti-IL1RAcP antibodies in psoriasis research. ***p < 0.001.
Experimental schedule for establishing a monosodium urate (MSU)-induced peritonitis model and in vivo efficacy evaluation of CAN10 and ALM27134 analogs in IL1RACP humanized mice. Male IL1RACP humanized mice received intraperitoneal (i.p.) injections of vehicle, CAN10 analog (10 mg/kg), or ALM27134 analog (10 mg/kg) on days 0 and 3. One hour after the initial administration on day 0, mice received an intraperitoneal injection of monosodium urate (MSU) to induce peritonitis. Samples were collected at the experimental endpoint for efficacy evaluation. MSU: monosodium urate.
Effects of anti-IL1RAcP antibodies on immune cell infiltration in peritoneal lavage fluid in a monosodium urate (MSU)-induced peritonitis model using IL1RACP humanized mice. (A) Quantification of mouse CD45⁺ (mCD45⁺) cells in peritoneal lavage fluid across treatment groups. (B) Total neutrophil counts in peritoneal lavage fluid. (C) Percentage of neutrophils among mCD45⁺ cells. Treatment with the in-house CAN10 analog (10 mg/kg) or ALM27134 analog (10 mg/kg) significantly reduced neutrophil infiltration, with neutrophil counts returning to levels close to those observed in the control group. Statistical significance was determined using two-way ANOVA. *p < 0.05, **p < 0.01, ****p < 0.0001.
Q1: What are IL1RACP humanized mice (B-hIL1RACP)?
IL1RACP humanized mice (B-hIL1RACP) are human IL1RACP gene-humanized mice on a C57BL/6 background, developed for IL1RACP-targeted inflammation and antibody efficacy research.
Q2: Why is IL1RACP important?
IL1RACP, also known as IL1R3 or IL-1RAcP, is a shared accessory receptor for IL1 family cytokine signaling, including IL1, IL33, and IL36 pathway responses.
Q3: How was human IL1RACP expression validated in IL1RACP humanized mice (B-hIL1RACP)?
Human IL1RACP mRNA was validated by RT-PCR, and human IL1RACP protein was validated in splenocytes by flow cytometry.
Q4: Can IL1RACP humanized mice (B-hIL1RACP) be used for antibody efficacy studies?
Yes. IL1RACP humanized mice (B-hIL1RACP) have efficacy data in IMQ-induced psoriasis-like skin inflammation and MSU-induced peritonitis models using anti-IL1RACP antibody analogs.
Q5: What are the main applications of IL1RACP humanized mice (B-hIL1RACP)?
Applications include IL1RACP-targeted antibody evaluation, IL1 family signaling research, autoimmune and inflammatory disease studies, psoriasis-like inflammation models, peritonitis models, and preclinical biologics development.
