• Cytokine Mouse Models
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    Cytokine Mouse Models

Cytokine Mouse Models


Cytokines are cell-to-cell signaling proteins that play a central role in immune development and responses, and its dysregulation is associated with a several diseases such as autoimmune and inflammatory disorders, chronic infections and even cancer. Applied StemCell offers research-ready, mouse models expressing humanized cytokine genes for studying the underlying mechanisms of immune response and inflammation as well as for immunotherapy and oncology efficacy studies and drug screening.

  • Knock-in of humanized counterparts of cytokine gene(s) into the endogenous locus.
  • In vivo and in vitro validated for physiological expression of human version of the genes (in-house and through collaborators).
  • Mouse models generated in the widely used C57BL/6J background.


Cytokine Mouse Models

Model Name Genes Gene Synonyms Human Orthologs
IL4RA-HU Il4ra Il4r; CD124 IL4R
IL17A-HU Il17a Il17 IL17A
IL6R-HU Il6ra CD126, IL-6R IL-6R
IL6-HU Il6 Il-6 IL6
IL9-HU Il9 P40, Il-9 IL9
IL23A-HU Il23a p19, IL-23 IL23A
Il5-HU Il5 Il-5 IL5
IL17F-HU Il17f C87042; IL-17F IL17F
IL3-HU Il3 BPA; PSF; HCGF; Il-3; MCGF; Csfmu IL3
IL6&IL6R-HU Il6; Il6ra Il-6; CD126, IL-6R IL6; IL-6R
IL7-HU Il7 Il-7; hlb368; A630026I06Rik IL7
IL3-HU Il3 BPA, Csfmu, HCGF, Il-3, MCGF, PSF IL3
IL1B-HU Il1b Il-1b; IL-1beta IL1B
IL2-HU Il2 IL-2 IL2
IL17RA-HU Il17ra Il17r; Cdw217; VDw217; AW538159 IL17RA
IL5RA-HU Il5ra Il5r; CD125; CDw125 IL5RA
IL2RA-HU Il2ra CD25; Il2r; Ly-43 IL2RA
IL3&CSF2-HU Il3; Csf2 BPA, Csfmu, HCGF, Il-3, MCGF, PSF; CSF; Csfgm; GMCSF; Gm-CSf; MGI-IGM IL3; CSF2
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Application Notes

Validation Data for Humanized IL6/IL6R Double Knock-in Mouse Model

Strain Name: C57BL/6-Il6tm1(hIL6)Il6raem1(hIL6R)/Asc Strain Background: C57BL/6

IL (interleukin)-6 is a pleiotropic cytokine that is critical for B cell differentiation and regulation of immune and inflammatory responses. IL-6 functions by forming a protein complex with the IL-6R (IL-6 receptor) and the ubiquitously expressed signal transducer receptor subunit, gp130 which triggers the JAK/STAT pathway. Dysregulation of the IL6 or IL6R expression has been implicated in several inflammatory diseases such as Castleman’s disease, rheumatoid arthritis, diabetes mellitus, and in autoimmune diseases and certain types of cancer.

We have generated a double knock-in mouse model where both the mouse endogenous Il6 and Il6R have been replaced with the human IL6 and IL6R genes. These double knock-in mouse models are ideal for evaluating the efficacy of potential immunotherapy drug combinations.


Figure 1. Quantitative PCR (qPCR) analysis of IL6 mRNA expression in liver tissue of humanized IL6&IL6R (IL6/IL6R-HU) homozygous mice and wild type mice. After LPS activation, the humanized IL6&IL6R mice showed elevated human IL6 mRNA and very low levels of mouse Il6 mRNA. In wild type C57BL/6 mice, LPS activation showed elevated mouse Il6 mRNA expression but not human IL6 mRNA.


Figure 2. Expression of IL6 in the serum of humanized IL6&IL6R homozygous mice (IL6/IL6R-HU) and wildtype C57BL/6 mice was measured by ELISA. The results showed that the expression of human IL6 in serum collected from humanized IL6&IL6R homozygous mice after LPS activation and no detectable levels of mouse Il6. In contrast, wildtype mice showed expression of mouse Il6 but not human IL6.


Figure 3. Expression of IL6R in humanized IL6&IL6R (IL6/IL6R-HU) homozygous mice and wildtype (C57BL/6) mice was measured by ELISA. Human IL6R expression was detected in serum, liver and pancreas collected from the humanized mice with significantly lower in wildtype mice.