The SRG Rat: An Emerging Model in the Research Model Rat Race

The severely immunodeficient SRG rat, with its unique phenotype and physiology, has certain advantages over immunodeficient mice

NOTE: This article is available in other languages (FRANÇAIS / DEUTSCH).

In 1906 at the Wistar Institute of Philadelphia, Henry Donaldson and Helen Dean King used selective inbreeding to pave the way for the standardization of the common laboratory rat . Most lab rat strains descended from the original Wistar colony, including Long-Evans and Sprague Dawley.

One recent descendant is the SRG OncoRat, a severely immunodeficient inbred rat with enormous utility for studying human cancer, infectious diseases, human tissue transplantation, and cellular therapies. Developed by Kentucky-based Hera BioLabs, the SRG rat offers numerous advantages over immunodeficient mice; its larger size enables larger tumor growth and easier surgeries. It is also more permissive to frequent tissue and serum harvests for downstream analysis than mouse models. Because the tumor uptake rate ranges between 80 and 100 percent, some users find it is possible to reach statistically significant results with 5-6 rats, compared to 8-12 mice.

Because the immunodeficient SRG rat lacks key mammalian B, T, and natural killer cells, it doesn’t mount an adaptive response to foreign tissue. This triple immunodeficiency allows the SRG rat to support the transplant and growth of a variety of human cells, from primary tumor to stem cells that are critical in the pursuit for new cancer treatments.

The development of genetically engineered mice in the 1970’s and 1980’s led to increased mouse usage in the biomedical sciences in the last few decades. However, new advances in gene editing have enabled targeted mutations in the rat genome. Chris Brenzel, Senior Director of Business Development and Gene Editing Solutions at Hera BioLabs, sees great potential for accelerated breakthroughs, predicting that “the rat model is coming back, especially in the realm of xenografting.”

The SRG rat model vs. highly immunodeficient mouse models

Cancer is a key target area for the SRG rat model “We can do pharmacokinetic studies in the rat, after a single dose, or we can do serial bleeds longitudinally over the course of a study to know the effects of treatment on biomarkers or serum proteins,” says Fallon Noto, PhD, Executive Director of R&D/In Vivo Services at Hera BioLabs. In addition, the tumors can grow much larger, almost up to 10 times the size of the mouse, and still be humane. That allows for a larger amount of tissue at the end of the study, and maybe a longer window of treatment.”

One study conducted jointly by Hera BioLabs and Case Comprehensive Cancer Center in Cleveland, Ohio, found that the SRG model outperforms the mouse at supporting the growth of certain prostate cancer cell lines. And because the SRG rat also supports humanization with PBMCs, you can collect a generous volume of predominantly T cells compared to humanized mouse models, the study found.

The SRG model is an excellent host for numerous cancers supports the growth of human, including kidney, liver, pancreatic, ovarian, brain, and colorectal. Many studies involve subcutaneous tumors, but labs are also branching out into orthotopic models—where the tumor is implanted in the tissue of origin. “We have a collaborator who has implanted liver cancer in the liver of the rat, and another collaborator who is growing glioblastoma in the brain of a rat,” says Noto. “Both have chosen to use the rat based on its size. You can introduce more cells and grow tissues more easily in the rats.”

The SRG rat model offers more options for researchers

Koh Meng Aw Yong, Scientific Product Manager with Charles River Laboratories’ Research Models Services, says the availability of the SRG model opens the door to more rat research. He says that until recently, the only immunodeficient rat model on the market was the RNU rat, developed 40 years ago through a series of matings involving eight inbred rat strains. “But it was only partially immunodeficient,” says Aw Yong. “With the popularity of the extremely immunodeficient NCG mouse, it makes sense for us to offer rats that are also highly immunodeficient.”

Earlier this year, Charles River, a provider of research models to laboratories around the world, signed an agreement with Hera Biolabs to breed, distribute, market, and sell the SRG rat. “We believe that the SRG will be invaluable in addressing our clients’ research needs when those needs are not met by other models currently used” says Aw Yong.

Aside from cancer, the SRG rat is ideal for understanding human skin infections, Noto says. A recent study published in Scientific Reports described engrafting human skin, autologous lymphoid tissues, and autologous hematopoietic stem cells into SRG rats. The study found that the rats were able to support skin infection following inoculation with a bacterium. It also concluded that co-engraftment of skin and immune cells into a single rodent model made them good platforms for studying human skin infections.

One advantage of the rat model is that they can tolerate multiple blood draws per week, Aw Yong says. “This means that you need fewer animals to collect your data. If I were to take readouts from four different animals, no matter how homogenous they were, there would still be differences. But from one animal, the data is way more consistent.”

“I would say the SRG immunodeficient rat is the most exciting rat model to come out of our company in a while,” says Aw Yong.