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)

 

Figure 1 - CD4 humanized mice

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.

Figure 2 - CD4 humanized mice

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.

Figure 3 - CD4 humanized 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.

Figure 4 - CD4 humanized mice

 

Ready to be shipped to your lab

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