CD4ヒト化マウス

品系バックグラウンド：C57BL/6J

品系説明：

• CD4はマウスの体内で正常な生理発現と調節モードを持っている：免疫細胞の分布とT補助細胞の活性は変わらない。
• マウスの標的遺伝子を発現しない。

研究の応用:

• このモデルはhCD4標的医薬の免疫健全なマウスの体内での有効性と安全性を評価するのに用いられる。
• 炎症、自己免疫疾患、免疫腫瘍学とHIV感染の分野に用いる。

モデル検証:

• CD4の発現検査

Figure1. 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.

• 免疫細胞の比率検査

Figure2. Unaltered immune cell distribution. Homozygous CD4 humanized mice display same frequencies of B cells, NK cells and T cells in spleen as the wildtype mice. 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.

• サイトカインの発現検査

Figure3. 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 humanized CD4 mice.

• lg型検査

Figure4. 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.