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Rag2-/-γc-/- Mouse-based Human Chimeric Model |
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| Dr. Akkina |
Drs. Speck and Luban |
Dr. Su |
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| Characteristics of Humanized Rodent Models |
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| Strain |
Balb/c-Rag2-/-γ c-/- |
Balb/c-Rag2-/-γ c-/- |
Balb/c-Rag2-/-γ c-/- |
| # mice/donor |
40/donor |
CD34+ cell isolation yields 1–2 × 106 cells/donor sufficient for 5–10 mice (1 litter) |
20–50/donor |
| Source of human cells |
Fetal liver |
Cord blood |
Fetal liver |
| Method of isolation |
Magnetic bead enrichment for CD34+ cells |
Magnetic bead enrichment for CD34+ cells |
CD34+ MACS kit |
| Pre-transplant treatment-mice |
Irradiation 350 rads; intrahepatic injection into newborns |
Irradiation 200 rads given twice 4 h apart; intrahepatic injection into newborns |
Irradiation 400 rad; intrahepatic injection into newborns |
| Pre-transplant treatment-cells |
SCF, IL-3, IL-6 |
None |
None or retroviral transduction |
| Time frame from construction to experimental use |
12 weeks |
12–16 weeks |
>12 weeks |
| Location of human hematopoiesis |
Bone marrow |
Not investigated |
BM, Spleen, LN |
| Location of human Thymopoiesis |
Mouse thymus |
Not investigated |
Mouse thymus |
| Reproducibility of engraftment (% mice engrafted) |
>95% |
More than 90% of mice show human cells in periphery; about 50% of mice have levels >10% huCD45+ cells |
>95% with >20% human CD45+ cells in blood |
| Identity of specific human leukocytes present |
T and B cells, DCs, monocytes/macrophages and some granulocytes |
B and T cells, monocytes, DCs |
All human leukocytes |
| Populated tissues |
Bone marrow, lymph nodes, thymus, spleen, liver, intestines, lungs |
Thymus, spleen, blood, MLN, BM, liver; to some extent: gut |
BM/thymus/spleen/LN (no significant Peyer's patches found) |
| Characteristics of HIV Infection of Humanized Rodent Models |
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| HIV-specific immune response |
Not detected |
Some minor B cell response (1/25 animals tested); no T cell response detected |
Low gag-specific responses/no IgG detected |
| Tropism/clade of infecting HIV |
R5, X4, dual-tropic |
YU-2 and NL4-3 |
R5-X4-dual or R5/clade B |
| Target cells infected |
CD4 T cells |
CD3+ cells and only occasionally non T cells such as CD68+ macrophages |
CD4 T and DC |
| Level of plasma HIV viremia |
~107 copies RNA/ml |
Up to 2 × 106 copies/ml |
105-106 copies/ml |
| Duration of the infection |
at least 14 months |
Up to 190 days; longest period followed |
>22 weeks |
| Replication kinetics |
Peak viremia at about 6 weeks followed by maintenance of viremia |
HIV RNA levels peak 2–6 wpi, thereafter viremia mostly stabilizes at lower levels. |
HIV RNA levels peaks at 2–3 (dual tropic) or 4–6 wpi (R5-tropic) |
| In vivo generation of ART resistance |
Not done |
Not tested |
Not known |
| Treatment of HIV Infection Using Humanized Rodent Models |
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| ART to block transmission |
Not done |
Not done |
Not done |
| Microbicide to block transmission |
Not done |
Not done |
Not done |
| ART to control replication |
Not done |
Not done |
Yes. |
| Emergence of resistance to ART |
Not done |
Not done |
Not done |
| Elimination of HIV reservoirs |
Not done |
Not done |
Not done |
| HSC gene therapy to protect progeny cells |
yes |
Not done |
Not done |
| CD4 T cell gene therapy to protect cells |
Not done |
Not done |
Not done |
| Immune-based Therapy of HIV Infection Using Humanized Rodent Models |
Not done |
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| Preventive HIV vaccines |
Not done |
Not done |
Not done |
| Treatment HIV vaccines |
Not done |
Not done |
Not done |
| Adoptive Anti-HIV Ig therapy |
Not done |
Not done |
Not done |
| Adoptive Anti-HIV CTL therapy |
Not done |
Not done |
Not done |
| Immunoadjuvent therapy |
Not done |
Not done |
Not done |
| Investigation of HIV Pathogenesis |
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| Contribution of HIV genes to pathogenesis |
yes |
Not done |
Env/Nef |
| HIV-mediated CD4-depletion-lymphoid |
yes |
yes |
Yes |
| HIV-mediated CD4-depletion-mucosal |
Not done |
Not done |
mesenteric LN, yes |
| Effects of co-factors on replication |
Not done |
Not done |
Not done |
| Effects of co-infection e.g. mTb on replication |
Not done |
Not done |
Not done |
| End organ dysfunction |
Not done |
Not done |
Not done |
Goldstein AIDS Research and Therapy 2008 5:3 doi:10.1186/1742-6405-5-3 |
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