General information

Development

On the F344/DuCrl rat background, the Rag2 and Il2rg genes were knocked out. The Rag2 gene is located on chromosome 3, and after knockout, rats are unable to produce mature B lymphocytes and T lymphocytes, exhibiting immune deficiencies in cellular and humoral immunity; Il2rg encodes a common receptor subunit for the cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, which are important for immune function, and the knockout of this gene results in severely reduced immune function in rats, especially the activity of NK cells is almost lost.

F344RG^® rats have normal fertility, no premature aging phenotype, and are currently recognized internationally as one of the tool rats with the highest degree of immunodeficiency and suitable for human cell transplantation.

Phenotype

1. The growth curve of F344RG^® rat

Fig1. The growth curve of F344RG^® rat

2. Immune cell detection

图2. 8-week-old F344RG® rats and wild-type F344 rats peripheral blood T, B, and NK cell testing

Results: By flow cytometric analysis, compared with F344 rats, F344RG^® rats have significantly reduced peripheral blood CD3⁺ T cells, CD161a⁺ NK cells, and CD45RA B cells, almost undetectable, indicating that F344G rats lack functional T, B, and NK cells, with the most severe degree of immunodeficiency.

3. Immunoglobulin analysis

Fig3. The peripheral blood immunoglobulin level of 8-week-old F344RG® rats

Results: By flow cytometric analysis, compared with F344 rats, F344RG^® rats have significantly reduced peripheral blood CD3⁺ T cells, CD161a⁺ NK cells, and CD45RA B cells, almost undetectable, indicating that F344G rats lack functional T, B, and NK cells, with the most severe degree of immunodeficiency.

4. Tumor growth curve

Fig8. Tumorigenicity Test in F344RG^® rats

A: OVCAR-3 (human ovarian cancer cells), B: LNCaP (human prostate cancer cells), C: 22RV1 (human prostate cancer cells), D: U251 (human glioma cells), and E: Orthotopic glioma model

Examples of F344RG^® rat studies

1. Constructing a human glioma model and evaluating the therapeutic effect of CAR-T cell therapy

Fig9. The suppressive effect of CAR-T therapy on glioblastoma

2. Toxicological studies in F344RG^® rats

Fig 10. Long-term toxicity test in F344RG^® rats

A: Survival, eye and corneal condition; B: Body weight, feed intake; C: Blood cell counts

Results: Female and male F344RG® rats aged 6-9 weeks had a very low mortality rate in control mice of both sexes, with no remaining lesions and no spontaneous tumors in the 26-week experiment.

3. F344RG^® Rats in distribution studies

Fig 11. Drug survivability of arthrocytic administration in rats with different degrees of immunodeficiency

A: SD rats，B: Nude rats，C: F344RG^® rats

Results: The higher the degree of immunodeficiency, the longer the survival of the administered local cells, with F344RG® rats having the longest drug survival compared to SD and nude rats.

F344RG^® rats applications

1. Human cell or tissue transplantation

2.Tumor and tumor stem cell research

3.ES and iPS cell research

4.Hematopoietic and immunology research

5.Human disease infection model research

6.Research and development of humanized animal models

7. Safety evaluation of cell therapy products

8.Tumor transplantation and efficacy testing for tumors that are difficult to operate surgically

9.Pharmacogenetic studies of human-specific protein drugs

Reference

1. Generation and Characterization of Severe Combined Immunodeficiency Rats. Mashimo, Tomoji et al. Cell Reports, 2012, 2(3): 685-694.