Lymph Node Metastasis Imaging Models
Supplemental Table 1: Immunodeficient mouse hosts
Genotype(Common Name) / Functional
T cells / Functional
B cells / Functional
NK cells / Characteristic Features / Advantages / Disadvantages
Foxn1nu
(Athymic Nude)# / / / NL/ / Athymic
Alteration of winged helix/forkhead transcription factor
Abnormal hair and nail development
Develop extrathymic T-cell function / Well-characterized, widely-used
Support growth of many types of cells and tumors
Subcutanteously transplanted tumors easily visible / Normal numbers of APCs & macrophages
Normal complement activity
No engraftment of human HSC's
NOD
(NOD) / + / + / / Immune-mediated type I diabetes
Defects in antigen presentation, T cell regulation, cytokine production, myeloid differentiation, complement C5 / Defects in innate immunity / Functional adaptive immunity
Prkdcscid
(SCID)# / NL/ / Mutated prkdc gene: involved in TCR and immunoglobulin gene rearrangement affecting differentiation of stem cells into mature lymphocytes
Develop leakiness with age
Increased radiosensitivity / Supports enhanced engraftment of allogeneic and xenogeneic cells, tissues, and tumors compared to Foxn1nu / Normal to elevated complement activity
Normal numbers of functional APC's & macrophages
Tendency to develop graft vs. host disease
High incidence of thymic lymphoma
NOD-Prkdcscid
(NOD/SCID)# / / Defects in cytokine production, NK cell lysis, macrophage lipopolysaccharide response, complement C5, myeloid differentiation
Resistant to diabetes
Develop low leakiness with age
Increased radiosensitivity* / Supports human hematolymphoid engraftment better than Prkdcscid / Suboptimal reconstitution with human HSC
High incidence of thymic lymphoma
NOD-Prkdcscid-Il2rdnull
(NSG)# / IL-2Rg chain deficiency: no high-affinity signaling through multiple cytokine receptors
Increased radiosensitivity / Excellent level of engraftment of human HSC
Easily engrafted with human immune system
Transplantation research uses
Does not develop thymic lymphoma / Absence of appropriate MHC molecules for T cell selection
Absence of some human-specific cytokines required for human cell development
NOD-PrkdcscidB2m
(NOD/SCID/Beta-2-Microglobulin)# / 1 / Lacks serum immunoglobulin
Does not express MHC class I molecules
Develop low leakiness with age
Increased radiosensitivity / Better engraftment of PBMC's and HSC's than NOD-Prkdcscid or NOD-Rag1
PBMC engraftment results in high levels CD4+ T cells and normalization of CD4: CD8 ratio / PBMC engraftment: high levels of T cells, low levels of B cells
Less efficient reconstitution with human cells and tissues than NOD-Prkdcscid-Il2rg
Hemochromatosis
High incidence of thymic lymphoma
PrkdcscidLystbg
(SCID/Beige)# / 2 / Defective granulocyte chemotaxis and reduced bactericidal activity / Good model for receipt of xenotransplants and for infectious disease studies / Prolonged bleeding time due to platelet storage pool deficiency
Rag1null
(Rag1)# / / Rag1: essential for V(D)J recombination needed to generate functional B and T cell antigen receptors
Phenotype resembles NOD/SCID
Radiation-resistant / Supports enhanced engraftment of allogeneic and xenogeneic cells, tissues, and tumors compared to Foxn1nu / Normal complement activity
Normal APC functions
NOD-rag1null
(NOD/Rag1)# / / Phenotype resembles NOD/SCID
Radiation-resistant / Engrafts human lymphoid cells and HSC's at high levels
Best for adoptive transfer of diabetogenic NOD lymphoid cells
Does not develop thymic lymphoma / High incidence of pre-B cell lymphomas with age
NOD-rag1-Prf1
(NOD/Rag1/perforin1)# / Prf1: critical component of NK and CD8+ lymphocytes lytic pathway
Radiation-resistant / Better engraftment of PBMC's and HSC's than NOD-Prkdcscid or NOD-Rag1
PBMC engraftment results in high levels CD4+ T cells and normalization of CD4: CD8 ratio / Less efficient reconstitution with human cells and tissues than NOD-Prkdcscid-Il2rg
High incidence of thymic lymphoma
#: SPF-requirement
*: Tolerates up to 4Gy radiation
1: Nearly absent NK cells
2: Decreased NK cell cytotoxicity
1