For more information about PLOS Subject Areas, click Here we report the first catalog of microbial genes in fecal samples from Sprague-Dawley rats. E) H&E staining and IHC staining for AR and PSA in VCaP tumor tissue from SCID/NCr mice and SRG rat. (Unpaired t-test, p-values: * < 0.05). Radiotherapy effectively treats cancers of the head and neck. [25] However, characteristic of the species, the rat will still use its sharp incisors to bite if it is handled improperly. 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). MIA-PaCa-2, HCC1954, and 786-O were gifted to Hera BioLabs in June 2018. Copyright: © 2020 Noto et al. 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. Originated in 1925 by Robert W. Dawley from a hybrid hooded male and a female Wistar rat. Data Availability: All relevant data are within the paper and its Supporting Information files. Yes Mouse models therefore are not always ideal for drug efficacy testing and downstream analyses such as pharmacokinetics, pharmacodynamics, and toxicology. PLOS ONE promises fair, rigorous peer review, 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. Primary patient NSCLC tissue and NSCLC-PDX tissue collected from mouse and rat were fixed in 10% neutral buffered formalin, processed, paraffin embedded, and sectioned. Isolated protein was quantified, normalized by the Bio-Rad assay (Bio-Rad), run on a 12% SDS-PAGE (Invitrogen, Life Technologies), and transferred onto Nitrocellulose Membranes (Bio-Rad). 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®). Blood was collected in K2EDTA tubes. Mott Children’s Hospital.PDX research was supported by the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558). Investigation, One of the most robust and well characterized mouse models is the non-obese diabetic (NOD) Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG mouse). Liver cytosolic fractions prepared from a pool of male Sprague Dawley rats. Oral Administration of Aloe vera Ameliorates Wound Healing through Improved Angiogenesis and chemotaxis in Sprague Dawley Rats (E-pub Ahead of Print) 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. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. The tissues were homogenized and passed through a 70 μm cell strainer to remove clumps. Excluded Flora and Restricted Flora™ SD rats are useful as health sentinels, clean fosters or where co-housed with immunodeficient/genetically modified models. PDF | Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). 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. Compared to NK cells in the wild-type rat (I; 10.1% CD161a+), the SRG rat has significantly reduced circulating NK cells (J; 0.5% CD161a+). 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). Citation: Noto FK, Sangodkar J, Adedeji BT, Moody S, McClain CB, Tong M, et al. In SCID/NCr mice, VCaP tumors engrafted in 60% of the mice but the growth kinetics were highly variable. 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. https://doi.org/10.1371/journal.pone.0240169.s003, https://doi.org/10.1371/journal.pone.0240169.s004, https://doi.org/10.1371/journal.pone.0240169.s005. Department of Obstetrics and Gynecology, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles In addition, SRG rats can also greatly reduce the time needed to establish a PDX bank and can produce sufficient tumor tissue in the first in vivo generation (P1) to make a full preclinical study possible in the subsequent passage (P2). The excellent reproductive performance of the Sprague Dawley model makes it a preferred choice for generating timed- pregnant females. Taconic received stock from the NIH Animal Genetic Resource in 1970. 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). Investigation, The SRG rat carries an eight base pair deletion in the Rag2 coding exon and a sixteen base pair deletion in the first coding exon of the Il2rg gene (S1 Fig). Rats were . All the cells were grown in a humidified incubator at 37°C with 5% CO2. All cell lines were originally purchased from ATCC. De-identified patient samples were provided to Hera Biolabs in DMEM + 10% FBS, 1% Penicillin/Streptomycin, 1% Amphotericin B. 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. Animals with body condition score of less than 2 were considered under-conditioned and recommended for veterinary assessment and if necessary, subsequent euthanasia. Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Affiliation 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. Origin: The Sprague Dawley® outbred model was developed by Sprague Dawley, Inc. NIH received stock from Sprague Dawley, Inc in 1945. The strain was created by R. W. Dawley in 1925, from a hooded male hybrid of unknown origin and an albino female (probably Wistar), and was crossed with the female’s progeny for 7 generations.The SPRAGUE DAWLEY® rat is an albino outbred rat with an elongated head … 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. All other mouse studies were performed in the NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ, strain 005557 from The Jackson laboratory). Spleen and thymus were collected in FACS buffer (BD Pharmingen 554656). These mouse models demonstrate markedly variable differences in human cancer cell line uptake and growth kinetics which broadly determine the feasibility of conducting cancer therapeutic efficacy studies. C-E) Quantification of data T cell populations, n = 3, error ±SD. [25] Conceptualization, 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). Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. Here we highlight growth kinetics of several human cancer cell lines and NSCLC-PDX samples in the SRG rat. Authors Ying Piao 1 , Yunen Liu, Xiaodong Xie. The SRG rat spleen was devoid of mature B cells, as assessed by cell surface markers CD45RA (B220) and IgM (Fig 1D–1F). Affiliations Flow cytometry dot plots show representative data from one WT and one SRG rat each. These measurements and all health observations were performed by trained animal care technicians and referred to veterinary staff if abnormalities were observed. e0240169. In vivo models are essential in determining the effectiveness and safety of potential treatments prior to clinical testing in patients. Knowing this cell line engrafts and grows poorly in the mouse and taking advantage of the size of the rat, we inoculated SRG rats with 10 x 106 cells (~40,000 cells/cm2 BSA). The Hsd:Sprague Dawley ® SD rat has a wide array of historical research use including in the field of cardiology. In comparison, mouse models may require multiple passages past the third or fourth before sufficient tumor-bearing animal numbers are produced for an efficacy study, increasing the risk of genetic drift from the original tumor. 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. P<0.05 was considered statistically significant. 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]. A strain, in reference to rodents, is a group in which all members are, as nearly as possible, genetically identical. Correlation measurements were obtained by Pearson Correlation. 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. The processed soybean meal was added to formulated rodent diets at 20% (w/w) and fed to rats for 90 days. Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan, United States of America, Growth kinetics of these human cancer cell lines have been tested by others in mouse xenograft models [21–24]. The experimental protocol for diabetic rat model establishment and drug administration was shown in Figure 1. Membranes were exposed to ECL (Roche) following the manufacturer’s instructions. 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. A) Tumor growth curve in NSG mice and SRG rats inoculated with 2x106 HCT-116 cells subcutaneously in the hind flank. Yes 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. (Unpaired t-test, p-values: ** < 0.01). The lack of thymus tissue in the SRG rat results in a low recovery of viable thymocytes. Division 22 of the American Psychological Association, TIP: The Industrial-Organizational Psychologist, Tutorials in Quantitative Methods for Psychology, https://psychology.wikia.org/wiki/Sprague_Dawley_rat?oldid=111932. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. shell extract in obesity induced Sprague Dawley rats. P1 is the initial passage in vivo in SRG rats. A : schematic representation of our exposure paradigm. We examined the growth of the human colorectal carcinoma cell line, HCT-116, in SRG rats in comparison to NSG mice. Contributed equally to this work with: A hot aqueous Efficient take rates combined with the 10 times larger tumor size make SRG rats a promising tool for establishing PDX lines for a variety of populations and/or cancer-types. Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) Animal technicians are trained through AALAS courses, including “Post-Procedural Care of Mice and Rats in Research; Minimimzing Pain and Distress”. 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. Food and water were provided ad libitum and nestlets or virgin kraft paper were provided in all cages for enrichment. Its main advantage is its calmness and ease of handling. 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. Writing – original draft, Affiliation We injected 2 x106 HCT-116 cells in Cultrex, an extracellular matrix protein isolated from Engelbreth-Holm-Swarm mouse sarcoma similar to Matrigel, into NSG mice and SRG rats. Its main advantage is its calmness and ease of handling. The rats … 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. Footshock could be avoided by pressing a lever during a danger period prior to onset of shock. The Ns for Fischer rats for (DI) water or 0.416, 0.5, 0.75, 1, 2, 5 or 10 mg/kg of ketanserin, respectively, were 5, 8, 9, 6, 10, 5, 13 and 7. No, Is the Subject Area "Non-small cell lung cancer" applicable to this article? VCaP tumors grown in SCID/NCr mice or SRG rats were collected, fixed in 10% neutral buffered formalin, processed, paraffin embedded, sectioned, and stained for AR (ab108341, abcam) or PSA (A056201-2, Dako). We inoculated VCaP cells in Cultrex into the flanks of SCID/NCr mice, 5 x 106 cells (~70,000 cells/cm2 BSA), in keeping with published parameters. Sprague -Dawley rats are commonly used strains of rats in experimental research due to their metabolic characteristics which are closer to the human and their ability to replicate many symptoms of human conditions (Cortés-Ortiz et al., 2014; Hubert et. Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. Try out the SAS Sprague Dawley rat with our animal model evaluation program→ Nurul Iftitah Musameh, Siti Rosmani Md Zin, Normadiah M. Kassim Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Abstract Genistein (Gen), is commonly consumed phytoestrogen among Asian and known to exert weak estrogenic effects. In the current exploration, different parts of bitter gourd were evaluated for their cholesterol lowering potential in cholesterol fed Sprague dawley rats. A549 (ATCC® CCL-185™), PC3 (ATCC® CRL-1435™), and LNCaP/AR were used as positive and negative controls. The SRG rat demonstrates efficient tumor take rates and growth kinetics with different human cancer cell lines and PDXs. SD rats are docile and are easy to handle. Red blood cells in tissues and blood were lysed by incubating with ACK Lysing Buffer (Quality Biological #118-156-721) for 10 minutes at room temperature. Excellent reproductive performance and maternal characteristics. These data suggest that knockout of Il2rg prevents the increase in NK cells in the spleen resulting in absence of circulating NK cells in the SRG rat. Animals were euthanized by CO2, with secondary methods including cervical dislocation (all mice and rats <200g) or thoracotomy (rats >200g) as approved by the IACUC and in accordance with current AVMA guidelines. Data curation, One such cell line is VCaP, a human prostate cancer cell line derived from a vertebral metastatic growth. Sprague Dawley Rat High Fat T Increases Pain Behaviors In Rats With Or Without Nutrients full text calorie restriction modulates 1209 s7 article 03 sprague dawley rats a model of successful heart aging sciencedirect an weights of sprague dawley rats and age table safety essment and single dose toxiiics of the flavouring This is in contrast to the SDR (Rag2 single knockout) rat, which has highly elevated NK cells compared to the wild-type rat [15]. To Charles River in 1950 from Sprague Dawley, Inc. We have demonstrated here that SRG rats can be used to establish NSCLC-PDX with 78% success as we were able to establish PDX banks from seven different patients of the nine patients sampled. The SRG rat also carries a 16bp deletion in the first exon of the Il2rg gene to knock out its function. If an animal loses greater than 20% initial body weight, they are euthanized. The study followed European Union regulations 86/609/EEC, 2010/63/EU for … Compared to B cells in a wild-type spleen, the SRG spleen contains no mature B cells as demonstrated by lack of CD45R (B220)+/IgM+ cells. Yes NSG mice are genetically engineered for knockout mutations in the Prkdc and Il2rg genes rendering the model B, T, and NK cell deficient [1–4]. 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 ®). Data is presented as mean ± standard deviation or mean ± standard error of the mean as noted in the figures. Body condition score was also assessed for mice and rats as previously described [17, 18]. Previously we reported a Rag2 (Recombination Activating Gene 2) knockout rat on the Sprague-Dawley strain (SDR rat) which is mature B cell deficient and severely depleted of T cells [15]. Division of Genetic Medicine, Department of Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles Although multiple immunodeficient rodent strains are available, some important human cancer cell lines exhibit poor tumor growth and high variability in those models. To assess their safety on the rat reproduction system, male Sprague Dawley rats were fed either glyphosate-tolerant (GM) soybean (40-3-2) or near-isogenic, non-GM (A5403) (control) soybean meal. studied the development of the hair follicle in individuals that displayed the hairless phenotype. Molecular analysis of VCaP tumors confirmed expression of the androgen receptor (AR) in both the SCID/NCr mouse and SRG rat models (Fig 4B and 4C). 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. 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. Genetic analyses were performed for three of the PDX lines at multiple passages for each line in addition to the original patient sample. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. Analysis of whole blood demonstrated that while a wild-type rat had 37.4% CD4+, 36.6% CD8+, 3.5% CD4+/CD8+ in the circulating lymphocytes (Fig 2A and 2C–2E), the SRG rat had significantly reduced populations at 1.6% CD4+, 5.3% CD8+, 1.2% CD4+/CD8+ cells (Fig 2B and 2C–2E). These primary patient tumor tissues, annotated as passage 1 or P1, were sectioned into 2mm x 2mm pieces and implanted subcutaneously on the flank of SRG rats or NSG mice using a 10G trocar. The average litter size of the Sprague Dawley rat is 10.5. Sprague-Dawley rats were anesthetized and exposed to saline or nicotine aerosol for 15 min and transferred to room air. (Unpaired t-test, p-values: **** < 0.0001). The strain was created by R. W. Dawley in 1925, from a hooded male hybrid of unknown origin and an albino female (probably Wistar), and was crossed with the female’s progeny for 7 generations.The SPRAGUE DAWLEY® rat is an albino outbred rat with an elongated head … PLoS ONE 15(10): Immunohistochemical analyses were used to further confirm the prostatic origin of these tumors. No, Is the Subject Area "Cancers and neoplasms" applicable to this article? Strikingly, circulating NK cells in the peripheral blood of the SRG rat are significantly reduced (0.5%) relative to wild-type levels (10.1%) (Fig 2I–2K). Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America, Formal analysis, This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley … The NSG mice had tumor volumes of 1000–2700 mm3 by 30 days post-inoculation and SRG rats had tumor volumes of 1800 mm3 to over 12,000 mm3 by 24 days post-inoculation (Fig 3A). `` colorectal cancer '' applicable to this work https: //doi.org/10.1371/journal.pone.0240169.s003, https: //doi.org/10.1371/journal.pone.0240169.s004, https //doi.org/10.1371/journal.pone.0240169.s003. Digital calipers 3 times a week advantage of sprague dawley rats parts of bitter gourd were evaluated for their cholesterol lowering potential cholesterol... 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