Rat Sprague Dawley Plasma from Innovative Research is manufactured using whole blood collections from Sprague Dawley rats. Origin: Established in 1925 by Robert Dawley, the original Sprague Dawley rat colony was obtained by Harlan in 1980 through the acquisition of Sprague-Dawley, Inc. Harlan became Envigo in 2015. It was for this reason, together with the growing use of APM in industrialized countries, that we designed and performed a mega-experiment using seven groups of Sprague-Dawley rats (100-150 per sex per group) treated with APM in feed at various dose levels (including one very close to the ADI for humans), from 8 weeks of age until natural death (Belpoggi et al. [1][2][3][4] Its main advantage is its calmness and ease of handling. Human VCaP (ATCC® CRL2876™), HCT-116 (ATCC® CCL247™), MIA-PaCa-2 (ATCC® CRL-1420™), HCC1954 (ATCC® CRL-2338™), and 786-O (ATCC® CRL-1932™) cells were a gift from Dr. Goutham Narla at the Case Comprehensive Cancer Center, Cleveland. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. Initial engraftment of the patient tumors resulted in tumor volumes of 4,000 mm3 by 75 days post-inoculation and tumor growth rate in SRG rats increased through serial passages (Fig 5A and S3A–S3F Fig). Spleen and thymus were collected in FACS buffer (BD Pharmingen 554656). In addition, SRG rats are highly permissive to engraftment with NSCLC-PDX tumors from patients. here. Our data demonstrate that the SRG rat has the potential to be a valuable model for evaluating drug efficacy in a wide range of human cancers. However, our data suggest that for certain cell lines, fewer rats are needed to achieve a treatment cohort of tumor-bearing animals and the animal numbers can be further reduced compared to mouse due to the ability to perform serial blood draws in the same rat throughout a single study. K) Images of wild-type Sprague Dawley and SRG rat spleen. SCID/NCr mice and SRG rats were inoculated with 5x106 and 10x106 VCaP cells, respectively, subcutaneously in the hind flank. Rederived into an isolator foundation colony in 1997. Its main advantage is its calmness and ease of handling. No, Is the Subject Area "Colorectal cancer" applicable to this article? All animals were monitored once daily, including weekends and holidays, for general health, activity level, body and tumor appearance, mobility, and ability to eat, drink, and groom within normal limits. Cardiology - Outbred Rats Established in 1925 by Robert Dawley, the original Sprague Dawley rat colony was obtained by Harlan in 1980 through the acquisition of Sprague-Dawley, Inc. Harlan became Envigo in 2015. https://doi.org/10.1371/journal.pone.0240169.g001. Data Availability: All relevant data are within the paper and its Supporting Information files. Department of Obstetrics and Gynecology, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles In contrast, all 6 tumor HCT116 xenografts in SRG rats reached 150–250 mm3 in volume by 10 days post-inoculation and exhibited faster growth kinetics compared with the mouse, with all tumors in the SRG rats reaching endpoints for size between 26 and 33 days after inoculation. The rationale for using this compound instead of the more active O6-benzylguanine and its substituted benzyl derivatives at the benzyl ring is its greater solubility in … al., 2000). These data demonstrate that SRG rats support the growth of human cancer cell lines with favorable take rates and growth kinetics for preclinical efficacy studies. The hairless mutation appeared in a SPRAGUE DAWLEY® colony in 2004; Bazzi et al. A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. All animal studies were conducted under the authorities of University of Kentucky’s and Icahn School of Medicine at Mount Sinai’s IACUCs, who specifically reviewed and approved these protocols. We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. There were no changes observed in motility or food intake in tumor bearing animals. 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. Patient derived lung tumor was implanted into SRG rats. For more information about PLOS Subject Areas, click C) Quantification of data, n = 3, error ± SD. Change trends of organ weight background data in sprague dawley rats at different ages J Toxicol Pathol. If ulceration occurs, antibiotic ointment, which may include an analgesic, is applied topically at the onset of ulceration to prevent infection after consultation and approval by veterinarians. The study followed European Union regulations 86/609/EEC, 2010/63/EU for … Sprague Dawley rats were first bred by the Sprague Dawley farm in Madison, Wisconsin in 1925 through multiple crosses with a single-hooded male and six albino female rats. All cell lines tested engrafted with 100% efficiency in SRG rats and grew well over the study period. Total protein concentration: 20 mg/ml We provide liver subcellular fractions from a variety of tox species, including human, nonhuman primates (Cynomolgus Monkey and Rhesus Monkey), dog (Beagle), rat (Sprague-Dawley), mouse (CD-1 and Balb-c), and trout (Oncorhynchus mykiss). https://doi.org/10.1371/journal.pone.0240169.g005. We found that a UVA dose of 15 J/cm 2 was dose and … Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Affiliation B) Tumor growth curve in SRG rats inoculated with 5 x106 MIA-PaCa-2 cells. Effects of genistein on male sprague dawley rats reproductive development. Furthermore, it has potential to function as a patient avatar whereby personalized genomically-guided precision therapies can be tested within a reasonable timeline to affect patient treatment. C) Western blotting for AR in tumor tissue from the SRG rat. The lack of thymus tissue in the SRG rat results in a low recovery of viable thymocytes. DNA extracted from flash frozen PDX tissue using a Qiagen kit (Qiagen #69504) was sent to the University of Michigan MMGL-Molecular Genetics core facility for genomic analysis. 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]. Published success rates for NSCLC-PDX establishment subcutaneously in mouse models are in the range of 20–40% which means even at best, the models fail for more than half of the patients [8–10]. Weight and tumor measurements (length and volume) were recorded 3 times weekly on Monday, Wednesday, and Friday. e0240169. For the purpose, four types of bitter gourd part i. e. whole fruit, seedless fruit, seeds, and seed extracts were used and compared with placebo in hypercholesterolemic rats. [5] This breed of rat was first produced by the Sprague Dawley farms in Madison, Wisconsin (later to become the Sprague Dawley Animal Company). for a 200 g rat, tumor volume cannot exceed 20,000 mm3). "Rats, Sprague-Dawley" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings).Descriptors are arranged in a hierarchical structure, which enables searching at various levels of specificity. Data represent average of 3 from each strain with SEM (Unpaired t-test, p-values: **** < 0.0001). For the original patient tumor and at each passage in the animals, a small piece was fixed in 10% neutral buffered formalin for histology and flash frozen in 2-methylbutane chilled on dry ice or liquid nitrogen for genomic analysis. Sprague-Dawley male rats weighing 120–140 g were housed in groups of two in clear plastic cages and maintained on a 12 h light/dark cycle (lights on 07:00–19:00 h) at °C with water and food available ad libitum. We further demonstrated that SRG rats have high engraftment rates, favorable growth kinetics for efficacy studies, and can support large tumor volumes, providing ample tissue for molecular characterization and PDX bank establishment. The last NSG mouse that achieved a tumor size sufficient for drug testing occurred at 16 days post-inoculation but had significantly slower growth such that it was under 900 mm3 at 40 days post-inoculation. In the NSG model, 4 of the 5 tumors reached dosing volume (150–250 mm3) by 12 days post-inoculation and displayed variable growth rates reaching volume endpoints (3000 mm3) between 28 and 40 days post-inoculation. 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]. If an animal loses greater than 20% initial body weight, they are euthanized. B) IHC staining for H&E, P40, and TTF1 in original patient tumor sample (3010), passage 1 of the same sample in SRG rat, and passage 2 of the same sample in SRG rat. 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. PLOS ONE promises fair, rigorous peer review, Moreover, patient-derived xenografts (PDX), in which tumor tissue is taken directly from the patient and grown in laboratory animals, may be more predictive than cell line-derived xenografts from established cell lines, as PDX models more closely recapitulate the histology and genomic features of the original tumor. SD rats have a white coat color (albino). Blood was allowed to clot at room temperature for at least 30 minutes, then centrifuged at 6000xg for 3 minutes at room temperature to separate serum. Correlation measurements were obtained by Pearson Correlation. Formal analysis, Each graph depicts tumor volumes for individual animals for 6 different NSCLC patient samples (A-F). To Charles River in 1996. Origin: Established in 1925 by Robert Dawley, the original Sprague Dawley rat colony was obtained by Harlan in 1980 through the acquisition of … Excluded Flora and Restricted Flora™ SD rats are useful as health sentinels, clean fosters or where co-housed with immunodeficient/genetically modified models. Cells were resuspended in 250 μL of each cell line’s respective culture media as listed in the Cell Culture methods. Analyses of Prostate Specific Antigen (PSA) in the serum showed a significant positive correlation to tumor volume in SRG rats with a 0.92 coefficient of correlation between serum PSA levels and tumor volume (Fig 4D). shell extract in obesity induced Sprague Dawley rats. 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. 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. Rats frequently develop various tumors, many of them malignant; the majority of tumors in the females develop in the mammary glands. https://doi.org/10.1371/journal.pone.0240169.g003. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America, Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. The tumors did not reach dosing volume until 50 days post inoculation with a highly variable 30 day window for dosing enrollment (Fig 4A and S2 Fig). Try out the SAS Sprague Dawley rat with our animal model evaluation program→ 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. The rat is the most commonly used rodent species for toxicology studies. If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan, United States of America, In addition, the presence of NOD strain polymorphisms in the signal-regulatory protein alpha (Sirpa) gene of the NSG mouse enhances human immune system engraftment for immuno-oncology studies [5–7]. 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. In addition, we can perform serial blood collection from the rat within humane guidelines to allow for pharmacokinetic and biomarker analysis following a single animal’s progression throughout the study. 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. D) Tumor growth curve in SRG rats inoculated with 10 x106 786-O cells. If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). This model has been tested and validated for use in oncology (SRG OncoRat®) with different human cancer cell lines and PDXs. By contrast, outbred populations are used when identical genotypesare unnecessary or a population with genetic variation is required, and these rats are usually referred to as stocks rather than … Genetic analyses were performed for three of the PDX lines at multiple passages for each line in addition to the original patient sample. Flow cytometry dot plots show representative data from one WT and one SRG rat each. Since the rat is often the preferred rodent species for preclinical studies due to size and robust nature, particularly for pharmacokinetic and toxicology assessments, a severely immunodeficient rat model could be highly advantageous for oncology studies. Poseida Therapeutics Inc., San Diego, California, United States of America, Affiliation Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) Subchronic feeding study of stacked trait genetically-modified soybean (305423 x 40-3-2) in Sprague-Dawley rats (held on an external server, and so may require additional authentication details) CropLife International fully acknowledges the source and authors of the publication as detailed above. By 10 days post-inoculation, tumor take rate was 100% in both NSG mice and SRG rats. If analgesics do not relieve pain as measured by clinical criteria mentioned above, the animal is euthanized. This model has been tested and validated for use in oncology (SRG OncoRat®). Several strategies have been utilized to develop genomic alterations in rats [12–14]. (Unpaired t-test, p-values: ** < 0.01). The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. Sprague-Dawley rats were treated with vehicle or rapamycin (2 mg/kg/day) for 15 days. Altogether, human tumor xenograft studies in SRG rats may significantly decrease the time required to collect preclinical efficacy results, while simultaneously collecting valuable biomarker data. 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]. Sudeh Izadmehr acknowledges support from the National Institues of Health Loan Repayment Program. Case Western Reserve University, Cleveland, Ohio, United States of America, Affiliation A-C) CD4+/CD8+ mature T cells in A) wild type control and B) SRG rat thymocytes. These rats were eventually used to study contraceptives. The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan … The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. In order to VCaP tumors surpassed 20,000mm3 (humane endpoint) by 4–5 weeks post-inoculation in SRG rats, reaching adequate size for study evaluation between 17–23 days after inoculation (Fig 4A). Sample 3067 (C) was implanted into SRG rats for P1 and then serially implanted into NSG mice for P2 and P3. Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. The excellent reproductive performance of the Sprague Dawley model makes it a preferred choice for generating timed- pregnant females. Additionally, the rat could be an alternative rodent model for cell lines that present significant engraftment and growth challenges in the existing mouse models. 2013 Mar;26(1):29-34. doi: 10.1293/tox.26.29. Taken together, SRG rats are a valuable addition to the existing mouse models for use in preclinical oncology research. The specific roles of these authors are articulated in the ‘author contributions’ section.” Support: Sequencing studies were carried out with the support of the Michigan Medical Genetics Laboratories in the Department of Pediatrics and the support of C.S. LNCaP/AR cells were a kind gift from Dr. Charles Sawyers (Memorial Sloan Kettering Cancer Center, New York, NY). Furthermore, studies have shown that genetic drift occurs across serial passages in vivo in transplanted PDXs as demonstrated by changes in the copy number alterations (CNA) landscape [11]. for a 200 g animal, the tumor cannot weigh more than 20 g = 20,000 mm3). broad scope, and wide readership – a perfect fit for your research every time. D) Compilation of PSA in the serum of SRG rat inoculated with VCaP cells correlates with tumor volume. Its main advantage is its calmness and ease of handling. Data is presented as mean ± standard deviation or mean ± standard error of the mean as noted in the figures. 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