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Table 3 Strains of immunocompromised mice used to develop the PDX-IM model

From: Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice

Mouse strain

Origin

Phenotype

Advantage

Shortcoming

Engraftment

Nude

Homozygous mutations in the Foxn1 gene

1. Thymus and hair are absent;

2. Antigen-presenting cells, macrophages, and NK cells are active

1. Well characterized;

2. Easy observation of subcutaneous tumors;

3. Low price

1. Functional B and NK cells;

2. T cell leakage increases with age

1. Low efficiency;

2. Not an ideal host

Rag1/Rag2

Rag1/2 recombinase defects

No mature T and B cells

Easy to evaluate DNA damaging therapies

1. NK cell activity is high;

2. Restrict HSC reconstitution in humans

Low efficiency

SCID

Mutations in the Prkdc gene

No mature T and B cells

Higher engraftment rate compared to nude

1. Functional NK cell;

2. Leakage of T and B cells;

3. The probability of death is very high;

4. Radiosensitive

1. Low efficiency;

2. Manily for prostate cancer

SCID/Beige

Combination of Beige mutation with the SCID mutation

1. No mature T and B cells;

2. Impaired Mφ and NK function;

3. Macrophage increase

Higher engraftment rate compared to SCID

1. Leakage of T cells;

2. Radiosensitive

1. Moderate efficiency;

2. Commonly used in F1

NOD/SCID

NOD (non-obese diabetic) mutation along with SCID

1. No mature T and B cells;

2. Impaired NK function and Mφ & DC

Better engraftment

1. Spontaneous lymphoma;

2. Short life span (av. 36 wks);

3. Radiosensitive

1. Moderate efficiency;

2. Manily for lung cancer and melanoma

NOD/SCID/IL2Rγnull

(NOG/NSG)

NOD/SCID mice with IL2/ receptor gamma truncation/disruption mutations

1. No mature T, B cells, and NK cells;

2. Impaired Mφ and DC

Excellent engraftment of PDX-IM including hematopoietic malignancies

1. Need strict SPF conditions;

2. Breeding is not easy;

3. Expensive

1. High efficiency;

2. Manily for breast, SCCHN and ovarian cancer

NOD/SCID/Jak3null (NOJ)

Backcrossing JAK3null mice with the NOD.Cg-Prkdcscid strain

1. No mature T, B cells, and NK cells;

2. Impaired Mφ and DC

1. Low incidence rate of lymphoma;

2. Longer life spans;

3. Suitable for low-growth tumors

1. Need strict SPF conditions;

2. Breeding is not easy;

3. Expensive

1. High efficiency;

2. Manily for breast, SCCHN and ovarian cancer

NOD-SCID-IL2RG − / − (NRG)

Rag1 mutation replaced the SCID mutation in NOG mice

1. No mature T, B cells, and NK cells;

2. Impaired Mφ and DC

1. Intra-oral injection for PDX-IM development;

2. Longer life spans (> 90 wks);

3. Low incidence rate of lymphoma

1. Macrophages, DCs and neutrophils influence engraftment efficacy;

2. GVHD development

1. High efficiency;

2. Manily for hormone receptor-positive (HR +) breast cancer;

3. Manily for human HSC engraftment

BALB/c

Rag2null/IL2Rγnull (BRG)

Rag2 null/Jak3 null (BRJ)

BRGSF

BALB/c mice with Rag2/IL2rg/Jak3 receptor gamma truncation/disruption mutations

No mature T, B cells, and NK cells

1. Excellent engraftment of PDX-IM;

2. Resistant to stress;

3. Easy breeding;

4. Resistance to radiation

Expensive

1. High efficiency;

2. Manily for cholangiocarcinoma, head and neck tumor, gastric cancer, bladder cancer, and hematological tumor

  1. NK natural killer cells, Mφ macrophages, DCs dendritic cells, SCCHN squamous cell carcinoma of the head and neck, GVHD chronic graft versus host disease, HSC hematopoietic stem cell