The SRG rat™ (SD-Rag2tm2hera Il2rgtm1hera), is a Sprague-Dawley rat with a double knockout for the Rag2 and Il2rgamma genes. This enhanced immunodeficient rat model has a severely impaired immune system lacking B-cells, T-cells, and NK-cells.
Improved engraftment enables oncology research
In mice many xenografts show low, non-existent or inconsistent engraftment efficiency. Engraftment efficiencies in 5-20% range are quite common; making it challenging or impossible to generate a cohort of animals with similar tumor sizes for an efficacy study. The SRG rat has demonstrated improved take rates and kinetics enabling effective in vivo studies using tumor models not previously feasible.
VCaP prostate cancer cells known to have poor engraftment rates and kinetics in immunodeficient mice (i.e. nude mice, SCID mice, NSG mice), thrived in the SRG rat. Preclinical studies with Enzalutamide against the VCaP tumor performed as expected. Download AACR Poster on Humanization.
Get to efficacy studies & data faster
The SRG rat grows ~10x larger tumors and produces larger samples for analysis. As such, patient derived xenograft (PDX) material may be expanded faster, getting to efficacy studies in fewer passages and a shorter amount of time in SRG rats.
When a cell line derived from an ovarian PDX model was transplanted SQ the take rate was 100% in both species but the tumor ten-fold bigger in the SRG rat compared with the NSG mouse, in the same amount of time. The SRG rat thus provides the possibility of getting adequate sample size from PDX tissue for an efficacy study faster than mouse. Download AACR Poster on PDX Models for more data.
The first humanized immune system rat
huPBMC-SRG rat™: SRG rats demonstrate robust immune-system humanization with peripheral blood mononuclear cells. Humanized SRG rats may have advantages in immuno-oncology, especially for tumor models with low take-rates in mice.
Human PBMCs were collected and injected into SRG rats for engraftment. By 4 weeks post-transplant, recipients had an average of 29% circulating human CD45+ cells. As of 10 weeks post-transplant, recipients have up to 46% human CD45+ cells and remain healthy. Download the AACR Poster on Humanization for full data.
More precise data and cost savings with efficacy & safety in one animal
The rat is a larger animal and is the preferred model for translational physiology and toxicology (Iannaccone & Jacob. Rats! Disease Models & Mechanisms. 2009;2(5-6):206-210). The rat’s size is appropriate for multiple dosing, particularly by routes other than oral, and for collection of multiple blood samples, which enable investigators to assess efficacy, systemic toxicity and PK/PD profile in a single animal over longer time periods. Traditionally, efficacy studies would take place in mouse models with the corresponding safety studies being conducted in rat; the resulting data comparisons are less than ideal.