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SCID Mouse and NOD/SCID mouse-based chimeric human models |
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| Dr. Stoddart |
Dr. Shultz |
Dr. Garcia-Martinez |
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| Characteristics of Humanized Rodent Models |
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| Strain |
C.B-17 scid/scid (Taconic) |
NOD-SCID IL2r gamma -/- |
NOD/SCID |
| # mice/donor |
50–60 mice/donor |
CD34+ cell isolation yields 1 × 106 cells/donor sufficient for engrafting 20- to 25 mice |
25 |
| Source of human cells |
Human fetal liver and thymus (20–24 g.w.) |
Umbilical cord blood; mobilized hematopoeitic stem cells |
Fetal liver/thymus |
| Method of isolation |
not applicable |
Magnetic bead enrichment |
Magnetic beads |
| Pre-transplant treatment-mice |
None |
100 cGy for newborns; 325 cGy for adults; Intravenous injection |
325 rads |
| Pre-transplant treatment-cells |
None |
None |
None |
| Time frame from construction to experimental use |
18 weeks |
12 weeks |
8–12 weeks |
| Location of human hematopoiesis |
Thy/Liv organ |
Bone marrow |
Bone marrow |
| Location of human Thymopoiesis |
Thy/Liv organ |
Mouse thymus |
Human thymic tissue |
| Reproducibility of engraftment (% mice engrafted) |
90–100% with >80% CD4+CD8+ |
>90% of newborn and adult mice are engrafted in the bone marrow, spleen and thymus |
>95% |
| Identity of specific human leukocytes present |
Immature and mature T cells, B cells, macrophages, plasmacytoid DCs |
B cells, T cells, conventional and plasmacytoid DCs, macrophages, monocytes, RBCs, platelets |
T and B cells, DCs, monocytes/macrophages, NK, NKT and Tregs |
| Populated tissues |
Human Thy/Liv organ |
Bone marrow, thymus, spleen, lymph nodes, intestine, blood |
GALT, Female and male reproductive tract, lung, bone marrow, lymph nodes, thymus, spleen, liver, peripheral blood. |
| Characteristics of HIV Infection of Humanized Rodent Models |
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| HIV-specific immune response |
None reported |
Work in progress |
Yes, human IgG |
| Tropism/clade of infecting HIV |
X4, R5, dual/mixed; clade B |
Not tested |
R5 and X4 |
| Target cells infected |
Intrathymic progenitors (CD3-CD4+CD8-), immature and mature thymocytes, macrophages |
Not tested |
CD4 T cells, monocytes/macrophages, DC |
| Level of plasma HIV viremia |
None to highly variable |
Not tested |
Variable depending on stain of virus and tropism |
| Duration of the infection |
5 weeks until severe depletion for X4 and dual/mixed; >6 months for R5 |
Not tested |
Variable depending on stain of virus and tropism |
| Replication kinetics |
Peaks at 3 weeks post infection (wpi) (X4 and dual/mixed), 6 wpi (R5) |
Not tested |
Isolate dependent |
| In vivo generation of ART resistance |
Not observed for NL4-3 and 3TC (no RT M184V) |
Not tested |
Not done |
| Treatment of HIV Infection Using Humanized Rodent Models |
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| ART to block transmission |
Not feasible |
Yes |
Not tested |
| Microbicide to block transmission |
Not feasible |
Yes |
Not tested |
| ART to control replication |
Yes, 4 classes of licensed ARVs so far. |
Yes |
Not tested |
| Emergence of resistance to ART |
Not observed for NL4-3 and 3TC (no RT M184V) |
Not done |
Not tested |
| Elimination of HIV reservoirs |
Not performed |
Not done |
Not tested |
| HSC gene therapy to protect progeny cells |
Not performed |
yes |
Not tested |
| CD4 T cell gene therapy to protect cells |
Not performed |
Not done |
Not tested |
| Immune-based Therapy of HIV Infection Using Humanized Rodent Models |
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| Preventive HIV vaccines |
Not feasible |
Yes |
Not tested |
| Treatment HIV vaccines |
Not feasible |
Not done |
Not tested |
| Adoptive Anti-HIV Ig therapy |
Feasible, but not performed |
Not done |
Not tested |
| Adoptive Anti-HIV CTL therapy |
Feasible, but not performed |
Not done |
Not tested |
| Immunoadjuvent therapy |
Not feasible |
Not done |
Not tested |
| Investigation of HIV Pathogenesis |
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| Contribution of HIV genes to pathogenesis |
Nef, Env (coreceptor usage), protease |
Yes |
Not tested |
| HIV-mediated CD4-depletion-lymphoid |
Thy/Liv organ |
Yes |
Not tested |
| HIV-mediated CD4-depletion-mucosal |
Not applicable |
Yes |
Not tested |
| Effects of co-factors on replication |
Not determined |
Yes |
Not tested |
| Effects of co-infection e.g. mTb on replication |
Not determined |
Yes |
Not tested |
| End organ dysfunction |
Thy/Liv organ undergoes severe thymocyte depletion |
Yes |
Not tested |
Goldstein AIDS Research and Therapy 2008 5:3 doi:10.1186/1742-6405-5-3 |
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