A current challenge in medical research is developing and choosing biologically appropriate models. In skin disorder research, the differences between human and animal skin, including absorption capacity, thickness, protein configuration, and DNA repair mechanisms is a significant limitation. Human Skin and Immune System (hSIS)-humanized NOD-scid IL2Rgnull (NSG) mouse and Sprague-Dawley-Rag2tm2hera Il2rgtm1hera (SRG) OncoRat® models are ideal animal hosts for studies on human skin. These rodents can support transplanted human skin, autologous lymphoid tissues, and liver derived hematopoietic stem cells for extended periods of time without graft vs host disease. These hSIS-humanized rodents are optimal animal models for research in skin-associated infections and diseases.

Why Are Humanized Rodents More Optimal?

The SRG rat was created through targeted-nuclease mediated gene disruption resulting in a loss of mature B, T, and NK cells. These SCID rats are an ideal model for combining efficacy, pharmacokinetic (PK), biomarker, and toxicology endpoints. While both NSG mice and SRG rats are capable of engrafting human tissue, the much larger size of the SRG rat is ideal for skin studies where a greater surface area improves study parameters.

Analysis of the human skin and lymphoid tissues engrafted into the SRG rat shows that the skin behaves normally, as if still growing on a human. Specifically, the skin is multilayered, able to grow human hair, and demonstrates robust wound healing. In addition to this, the lymphoid tissue exhibits a microanatomy comparable to the adult human thymus and spleen.1 Figure 1 displays the healthy development of full-thickness human skin and lymphoid tissues.

Figure 1: Development of human skin and lymphoid tissues in hSIS-humanized SRG rat model.

An example of how hSIS-humanized rodents are optimal for studying skin related disease is their ability to acquire methicillin-resistant Staphylococcus aureus (MRSA) infection and skin pathology. A research limitation for studying MRSA is that, until now, rodents could not be affected with MRSA for study purposes. In the SRG Rat, transplanted human skin can be infected with MRSA, showing normal pathological and histological disease patterns. MRSA is a serious health concern especially due to drug resistance; finding optimal animal models to test novel therapeutics is an ongoing need.1 Figure 2 shows the ability to use hSIS-humanized SRG rats for research—after inoculation of community associated (CA) CA-MRSA, humanized skin on SRG rats have histologically normal CA-MRSA.

Figure 2: Humanized SRG Rat skin supports CA-MRSA infection; CA-MRSA was inoculated into engrafted human skin and developed pathological and histologically normal CA-MRSA infection.

Hera’s Animal Models

Hera prides itself in producing animal models that provide the best in vivo data, while utilizing the fewest number of animals. Through improved engraftment rates and increased tumor volume, using the SRG rat can reduce the number of animals used per study. The SRG rat is an ideal xenograft host model, enabling a plethora of research options in preclinical oncology studies. In addition, pharmacokinetics and toxicology testing can be completed in a tumor bearing animal, improving efficiency and reducing the need for any cross-species assessment.

The hSIS-humanized SRG rat, once co-transplanted with full-thickness fetal human skin, autologous fetal thymus and liver tissues, and fetal-liver derived hematopoietic stem cells, becomes a novel model that is ideal for skin, immune, and immuno-oncology research. This model enables scientists to study many human diseases associated with the skin, including skin cancers, viral infections, and bacterial infections including human specific diseases such as MRSA.

Using the SRG rat for your preclinical research is an exciting next step in the future of biologically relevant animal models, especially in skin related diseases and oncology. Hera is offering innovative technology to researchers in both academia and industry to provide in vitro and in vivo services.  Hera prides itself on scientific rigor, dedication to our customers, and our state-of-the-art facility in beautiful Lexington, KY with a private vivarium and laboratory facilities. Contact us to learn more.