Humanized CD4 Mouse Model for In Vivo Preclinical Studies

Applications: Inflammation, autoimmune diseases, immuno-oncology, HIV infection

The human CD4 mouse model allows in vivo efficacy and safety assessment of anti-human CD4 compounds.

Model features:

  • No expression of murine CD4 (Fig. 1)
  • No physiological deregulation: Unaltered immune cell distribution, and T helper cell activity

Model validation

Unaltered immune response and T helper activity in CD4 humanized mice

  • Lymphocyte, NK and B cells distribution is similar to wild-type (WT) mice (Fig. 2)
  • Cellular response (e.g., cytokine expression) is normal as in WT mice (Fig. 3)
  • Humoral immune response is normal as in WT mice (Fig. 4)

 

Human CD4 replaces mouse CD4 expression

Fig. 1) Human CD4 replaces murine CD4.

Homozygous CD4 humanized mice display human-CD4 expression in PBMC. No murine CD4 expression is observed.

Blood samples from wild-type and homozygous CD4 humanized mice stained with a combination of mAbs (anti-murine CD4, anti-human CD4) and analyzed by flow cytometry.

Immune cell distribution in human CD4

Fig. 2) Unaltered immune cell distribution.

Homozygous CD4 humanized mice display same frequencies of B cells, NK cells and T cells in spleen.

Splenocytes are stained with different mAb combinations to assess frequencies of lymphocyte subsets measured by flow cytometry. Grey bars represent values for wild-type mice and hatched bars represent values for CD4 humanized mice.

Conserved cytokine expression profile in human CD4 mice

Fig. 3) Conserved cytokine expression profile.

Homozygous CD4 humanized mice display similar cytokine expression after ConA stimulation.

IL-2, IFN-γ and IL-4 concentrations in culture supernatants of mouse splenocytes stimulated with Con A are measured by using a 3-Plex Luminex kit. Black bars represent values for wild-type mice and hatched bars represent data for CD4 humanized mice.

Fig. 4) Similar Ig production.

Homozygous CD4 humanized mice display similar anti-KLH isotyping to wild-type mice.

Anti-KLH specific IgG1, and IgG2b polyclonal antibodies are assessed by sandwich ELISA in the serum of mice at day 28 after immunization with KLH and CFA. Serum samples from wild-type (WT) or homozygous CD4 humanized mice (HO CD4) were tested at different dilutions plotted against OD values.

Conserved cytokine expression profile in human CD4 mice

 

Ready to be shipped to your lab

  • Available onto C57BL/6J genetic background
  • Health-certified prior to delivery: SOPF/VAF Elite (Specific and Opportunistic Pathogen-Free/Virus- and Antibody-Free)
  • Worldwide delivery using logistic networks of renowned professional breeders

Access conditions

  • Freedom to operate for basic and pharmaceutical research
  • Generated data are the exclusive property of the customer and royalty-free
  • The model is available through in-licensing (flat annual fee, depending on company size)
  • On-demand production of cohorts by contract breeding