In order to overcome these deficiencies, we have created a rat with a functional deletion in both the Rag2 and Il2rg genes on the Sprague-Dawley background (SRG rat) that lacks B, T, and NK cells. Our data also demonstrate SRG rats support PDX engraftment and may accelerate the timeframe for PDX propagation and preclinical efficacy studies. Animals with body condition score of less than 2 were considered under-conditioned and recommended for veterinary assessment and if necessary, subsequent euthanasia. Analgesics (meloxicam or carprofen) are administered as needed to manage suspected pain. Since recent studies have shown that with each successive passage in vivo, tumors become more divergent genetically from the parent tumor, shortening the number of passages required to conduct an efficacy study will reduce animal numbers, associated costs, and ensure the tumors are more closely related to the parent tumor to better predict drug outcomes [11]. (Unpaired t-test, p-values: **** < 0.0001). All cell lines tested engrafted with 100% efficiency in SRG rats and grew well over the study period. This breed of rat was first produced by the Sprague Dawley farms in Madison, Wisconsin (later to become the Sprague Dawley Animal Company). https://doi.org/10.1371/journal.pone.0240169, Editor: Francesco Bertolini, European Institute of Oncology, ITALY, Received: July 6, 2020; Accepted: September 22, 2020; Published: October 7, 2020. J) Image of wild-type Sprague Dawley versus SRG thymus. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. Its main advantage is its calmness and ease of handling. Fallon K. Noto, C) Quantification of data, n = 3, error ± SD. Citation: Noto FK, Sangodkar J, Adedeji BT, Moody S, McClain CB, Tong M, et al. This product is manufactured in large batches, and is not available with any special instructions - if you require custom-collected material, please see our Innovative Grade US Origin Rat Sprague Dawley Plasma. Immunodeficient mice have proven essential for the establishment of in vivo human tumor models. Hera Biolabs, Inc. provided support in the form of salaries for authors (FKN, BTA, SM, CM, JC, TYJ) and Poseida Therapeutics, Inc. provided support in the form of salaries for authors (EO, MT), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Methods: Male Sprague Dawley rats were studied with either 20% fructose or 20% glucose in the drinking water and normal salt (0.4%) or high salt (4%) in the chow resulting in four dietary groups: fructose normal Fru+NS or high salt (Fru+HS) or glucose with normal (Glu+NS) or high salt (Glu+HS). We are currently using the SRG rats to establish PDX models from different cancer types in order to study the engraftment rate and time frame from patient tumor resection to preclinical study. To Charles River in 1996. Regional Medical Center, San Jose, California, United States of America, Affiliation A-C) CD4+/CD8+ mature T cells in A) wild type control and B) SRG rat thymocytes. (2020) The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. These rats were eventually used to study contraceptives. In primary spontaneous tumors and lymphomas virus particles cannot be found on electron microscopic examination; transmission of the tumors by filtered extracts has not been successful. Data in Fig 5 are from a single NSCLC patient tissue sample that was established as a PDX model in SRG rats (referred to as PDX 3010), however the data demonstrating congruency in immunohistochemistry are representative of the PDX lines we have established. G-I) NK cells in G) wild-type rat spleen and H) SRG rat spleen. Tumors were placed on the dorsal side of the flank so that they did not interfere with normal mobility or ability to nest properly. While patient derived xenograft (PDX) models are a valuable cancer model, there are some limitations in employing such model systems for precision medicine approaches. Tumors were monitored once daily for signs of ulceration. In summary, we have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B and T cells and circulating NK cells. Jaya Sangodkar, Roles and prepared for stereotaxic infusion of drug (0–10 nmol ferrous citrate and/or 0–16.8 nmol GSNO in 1 μl sterilized Ringer's solution or 0–33.6 nmol peroxynitrite in 1.05 μl 0.3 M NaOH solution) into right or left substantia nigra compacta area (i.n. Sample 3067 (C) was implanted into SRG rats for P1 and then serially implanted into NSG mice for P2 and P3. Low engraftment rates and slow growth for certain cancers like human non-small cell lung cancer (NSCLC) make it challenging to create these PDX models [8–10]. Each graph depicts tumor volumes for individual animals for 6 different NSCLC patient samples (A-F). Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. Sudeh Izadmehr acknowledges support from the National Institues of Health Loan Repayment Program. P1 is the inital implant into animals using fresh patient tissue, P2 is the first serial passage from animal to animal, P3 is the second serial passage from animal to animal. VCaP and MIA-PaCa-2 cells were grown in Advanced DMEM (ThermoFisher #11995065) with 10% fetal bovine serum (Atlanta Biologicals # S12450) and 1% penicillin and streptomycin solutions (Cat# 15140–122, ThemoFisher). SAS Sprague Dawley Rat Details. Animal technicians are trained through AALAS courses, including “Post-Procedural Care of Mice and Rats in Research; Minimimzing Pain and Distress”. seed extract at different dosages of 5 mg/kg, 25 mg/kg, and 125 mg/kg in Sprague Dawley rats, whereby it positively affected the body weight, caloric intake, lipid profile, and histopathology [10]. Similar to the SRG rat spleen, the SRG rat circulating blood was devoid of mature B cells, assessed by cell surface markers CD45RA (B220) and IgM (Fig 2F–2H). The caveat to using the rat for efficacy studies is the need for larger amounts of dosing materials. Membranes were probed with GAPDH (sc-32233, Santa Cruz) and AR (ab74272, Abcam). Outbred Rats - Hsd:Sprague Dawley SD - 002. F) Quantification of data, n = 3, error ± SD. Antibodies used were PE mouse anti-rat IgM (BD Pharmingen #553888), APC Mouse anti-rat CD45R (Biolegend #202314), PE Mouse Anti-Rat CD8a (BD Pharmingen #559976), APC Mouse Anti-Rat CD4 (eBioscience #17-0040-80), and APC Mouse Anti-Rat CD161a (Biolegend #205606). CropLife International fully acknowledges the source and authors of the publication as detailed above. These preclinical models provide critical information on the toxicity and efficacy of novel drugs and allow researchers to identify and address potential areas for further pharmacological and biological optimization. There were no changes observed in motility or food intake in tumor bearing animals. The SRG rat is completely devoid of circulating mature B cells (G) compared to wild-type (F). Immunohistochemical analyses of the tumors from the original patient sample and subsequent passages in SRG rats revealed comparable expression of p40 and thyroid transcription factor 1 (TTF1) confirming that the tumor maintained its histology in vivo (Fig 5B). Overall, SRG rats demonstrated favorable take rate and growth kinetics for downstream efficacy studies. In this report, we characterized a Rag2, Il2rg double knockout rat model on the Sprague-Dawley strain, the SRG™ rat, and demonstrated that it is a competent host for human cancer cell lines, PDX modeling, and drug efficacy studies in oncology (SRG OncoRat®). The rats are maintained as an outbred closed colony. for a 200 g rat, tumor volume cannot exceed 20,000 mm3). Yes Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America, Affiliation Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) Liver cytosolic fractions prepared from a pool of male Sprague Dawley rats. shell extract in obesity induced Sprague Dawley rats. Splenocytes, thymocytes, and whole blood were collected from wild-type and SRG rats and analyzed by flow cytometry to characterize the immune cell populations. Two tailed t-tests (for two group comparisons) was used for experiments. Origin: Established in 1925 by Robert Dawley, the original Sprague Dawley rat colony was obtained by Harlan in 1980 through the acquisition of … Tumor volume was calculated as (L x W2)/2, where width and length were measured at the longest edges [19, 20]. In immunodeficient mouse strains with Wistar rats health Loan Repayment Program if abnormalities were observed are essential in determining effectiveness... Your research every time in Figure 1 kinetics of these capabilities into the clinic of! F ) wild-type rat spleen the cell culture methods T cells in a high-quality journal to Charles River in from... 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