B-hIL17A/hIL17F/hIL17RA/hIL17RC mice

C57BL/6-Il17atm1(IL17A)Bcgen Il17ftm1(IL17F)Bcgen Il17ratm1(IL17RA)Bcgen Il17rctm1(IL17RC)Bcgen/Bcgen • 114047

B-hIL17A/hIL17F/hIL17RA/hIL17RC mice

Catalog Number: 114047
Strain Name: C57BL/6-Il17atm1(IL17A)Bcgen Il17ftm1(IL17F)Bcgen Il17ratm1(IL17RA)Bcgen Il17rctm1(IL17RC)Bcgen/Bcgen
Strain Background: C57BL/6
NCBI gene ID: 23765,3605,112744,84818 (Human)
Aliases: CD217; IL17R; IMD51; CANDF5; CDw217; IL-17RA; hIL-17R; IL17; CTLA8; IL-17; ILA17; CTLA-8; IL-17A; ML1; ML-1; IL17A; CANDF6; IL-17F; CANDF9; IL17RL; IL17-RL
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B-hIL17A/hIL17F/hIL17RA/hIL17RC mice

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  • Description
  • Targeting strategy
  • Phenotypic analysis
  • Efficacy

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    출판물

      Description

      B-hIL17A/hIL17F/hIL17RA/hIL17RC mice were obtained by mating B-hIL17A/hIL17F mice (120554) and B-hIL17RA/hIL17RC mice (120555). For validation data of this mouse model, you can refer to the validation data from the related gene humanized mouse models.

      Targeting Strategy

      IL17A 

      The exons 1-3 of mouse Il17a gene that encode the extracellular domain were replaced by human IL17A exons 1-3 in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. 

      The endogenous mouse promoter, 5′ UTR, and 3′ UTR regions are retained, allowing human IL17A expression to be driven by the native mouse Il17a promoter, while endogenous mouse Il17a transcription and translation are abolished.

      IL17F

      The exons 2-3 of mouse Il17f gene that encode full-length protein were replaced by human IL17F exons 2-3 in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. 

      The endogenous mouse promoter, 5′ UTR, and 3′ UTR regions are retained, allowing human IL17F expression to be driven by the native mouse Il17f promoter, while endogenous mouse Il17f transcription and translation are abolished.

      IL17RA

      The exons 2-9 of mouse Il17ra gene that encode the extracellular domain were replaced by human IL17RA exons 2-9 in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.

       The endogenous mouse promoter, 5′ UTR, and 3′ UTR regions are retained, allowing human IL17RA expression to be driven by the native mouse Il17ra promoter, while endogenous mouse Il17ra transcription and translation are abolished.

      IL17RC

      The Chimeric IL17RC CDS CDS that encodes human IL17RC signal peptide and extracellular domain, mouse Il17rc transmembrane and cytoplasmic domain was inserted after the 5’UTR of mouse IL17rc gene in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. 

      The chimeric IL17RC protein expression will be driven by endogenous mouse Il17rc promoter, while mouse Il17rc gene transcription and translation will be disrupted.

      Protein Expression

      Mouse IL17F was detectable in wild-type mice. Human IL17F was detectable in homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.

      Strain specific IL17F expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hIL17A/hIL17F/hIL17RA/hIL17RC mice by ELISA. Th17 cell culture supernatant was collected from wild-type C57BL/6 mice (+/+) (male, n=3, 9-week-old) and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice (H/H) (male, n=3, 9-week-old). Expression level of mouse and human IL17F were analyzed by ELISA (anti-mouse IL17F ELISA kit: R&D, DY2057; anti-human IL17F ELISA kit: Biolegend, 435707). Mouse IL17F was only detectable in wild-type C57BL/6 mice. Human IL17F was exclusively detectable in homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice (n=3). Values are expressed as mean ± SEM. ND: Not detected.

      Human IL17RC was detectable in wild-type C57BL/6JNifdc mice and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. The anti-human IL17RC antibody were cross-reactive between human IL17RC and mouse IL17RC.

      Strain specific IL17RC expression analysis in homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice (H/H;H/H;H/H;H/H), and analyzed by flow cytometry with species-specific anti-human IL17RC antibody (RD, FAB22691P). Human IL17RC was detectable in wild-type C57BL/6JNifdc mice and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. The anti-human IL17RC antibody were cross-reactive between human IL17RC and mouse IL17RC.

      Human IL17RC was detectable in wild-type C57BL/6JNifdc mice and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. The anti-human IL17RC antibody were cross-reactive between human IL17RC and mouse IL17RC.

      Strain specific IL17RC expression analysis in homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice by flow cytometry. Bone marrow were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice (H/H;H/H;H/H;H/H), and analyzed by flow cytometry with species-specific anti-human IL17RC antibody (RD, FAB22691P). Human IL17RC was detectable in wild-type C57BL/6JNifdc mice and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. The anti-human IL17RC antibody were cross-reactive between human IL17RC and mouse IL17RC.

      mRNA Expression Analysis in Colon

      Strain specific analysis of IL17RC mRNA expression in wild-type C57BL/6JNifdc mice and B-hIL17A/hIL17F/hIL17RA/hIL17RC mice by RT-PCR. Colon RNA was isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice(H/H; H/H; H/H; H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human IL17RC primers. Mouse Il17rc mRNA was only detectable in wild-type mice. Human IL17RC mRNA was exclusively detectable in homozygous B-hIL17A/hIL17F/hIL17RA/hIL17RC mice but not in wild-type mice.

      In Vivo Efficacy of Anti-human IL17A/F and Anti-human IL17RA Antibodies in Psoriasis Model

      Human IL-23 induces psoriasis model in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.
      (A) Experimental schedule for hIL23-induced psoriasis model in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. Mice (female, 8 week-old, n=6) were stimulated with hIL-23 on the ear fromDay 0 to Day 8 to induce psoriasis model , and brodalumab-analog (in house) and bimekizumab-analog (in house) were administered on Days -1, 2, 5, and 8.

      •  Treatment with brodalumab-analog and bimekizumab-analog significantly alleviated hIL-23-induced ear thickening, demonstrating potent therapeutic efficacy against psoriasis in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.

      Human IL-23 induces psoriasis model in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.
      (A) Absolute body weight (g) during treatment. (B) Body weight change (%) during treatment. (C) Absolute ear thickness (mm) during treatment. (D) Relative ear thickness change (%)during treatment. Treatment with brodalumab-analog and bimekizumab-analog significantly alleviated hIL-23-induced ear thickening, demonstrating potent therapeutic efficacyagainst psoriasis in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice. Values are expressed as mean ± SEM.

      •  Brodalumab-analog and bimekizumab-analog had therapeutic effects on psoriasis skin lesions in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice, confirming that B-hIL17A/hIL17F/hIL17RA/hIL17RC mice provide a powerful model for in vivo evaluation of anti-human IL17A/F and anti-human IL17RA antibodies. 

      Amelioration of hIL-23-induced psoriasis-like skin pathology in B-hIL17A/hIL17F/hIL17RA/hIL17RC mice.
      Ears were collected at the endpoint and stained with Hematoxylin and eosin (H&E). (A) H&E staining of the ear. (B) Histological changes were scored. (C) Epidermal thickness of themice. Results indicated that brodalumab-analog (in house) and bimekizumab-analog (in house) had therapeutic effects on psoriasis skin lesions in B-hIL17A/hIL17F/hIL17RA/hIL17RCmice, confirming that B-hIL17A/hIL17F/hIL17RA/hIL17RC mice provide a powerful model for in vivo evaluation of anti-human IL17A/F and anti-human IL17RA antibodies. Values areexpressed as mean ± SEM.

      * When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-hIL17A/hIL17F/hIL17RA/hIL17RC mice] (Cat# 114047) was purchased from Biocytogen.