Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. 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]. Studies were conducted after Institutional Animal Care and Use Committee approval and in strict compliance with institutional regulatory standards and guidelines. SAS Sprague Dawley Rat Details. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. P<0.05 was considered statistically significant. MIA-PaCa-2, HCC1954, and 786-O were gifted to Hera BioLabs in June 2018. Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) Epub 2013 Apr 22. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. By 10 days post-inoculation, tumor take rate was 100% in both NSG mice and SRG rats. Tumor volume was calculated as (L x W2)/2, where width and length were measured at the longest edges [19, 20]. Immunohistochemical analyses were used to further confirm the prostatic origin of these tumors. PDF | Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. Data represent average of 3 from each strain with SEM (Unpaired t-test, p-values: **** < 0.0001). [1][2][3][4] Its main advantage is its calmness and ease of handling. Affiliations Download. broad scope, and wide readership – a perfect fit for your research every time. Germinated rough rice crude extract calculation of rat breathing rate based cd sprague dawley igs rat charles mung bean starch rs 3 on the obesity calorie restrictionRat Weight Age Chart Buna DigitalfuturesconsortiumCd Sprague Dawley Igs Rat Charles RiverAn Weights Of Sprague Dawley Rats And Age TableRat Weight Age Chart Buna DigitalfuturesconsortiumMlac WrTypical Growth Curves For … Sprague-Dawley rats were anesthetized and exposed to saline or nicotine aerosol for 15 min and transferred to room air. Oral Administration of Aloe vera Ameliorates Wound Healing through Improved Angiogenesis and chemotaxis in Sprague Dawley Rats (E-pub Ahead of Print) 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). Funding: NCI contract HHSN261201700017C supported PDX establishment and their molecular and histological characterizations, along with their drug response studies. Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. 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). 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). 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). PLoS ONE 15(10): F) Quantification of data, n = 3, error ± SD. Blood was collected in K2EDTA tubes. Future uses for this model include developing a better understanding of the efficacy and toxicity of drug therapies and allowing for consistent and rapid translation from genomic findings to proof of concept in vivo studies. Outbred Rats - Hsd:Sprague Dawley SD - 002. Other criteria warranting euthanasia are ulceration on greater than 25% of the surface or perforation in any size ulceration that causes exudate or infection. No, Is the Subject Area "Colorectal cancer" applicable to this article? 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. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan Sprague Dawley) in January 1980.[6]. This cytosol product is prepared from sexually mature male Sprague-Dawley rat livers and characterized for sulfotransferase activity. Graphpad Prism 7 was used to perform all statistical analyses. The tissues were homogenized and passed through a 70 μm cell strainer to remove clumps. 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+). “Hairless” rats have hair shafts shaped like a lance head (“lanceolate”). SD rats have a white coat color (albino). In order to evaluate the genomic instability of the PDX model, we performed next-generation sequencing after passages 1, 2 and 3 in SRG rats using a panel of 6000 genes, which are associated with a variety of cancers, for three of the seven PDX lines created (Table 2). 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. Writing – original draft, Affiliation The SRG rat demonstrates efficient tumor take rates and growth kinetics with different human cancer cell lines and PDXs. Cells were stained with fluorophore-labeled antibodies at a final concentration of 25 μg/mL in 20 μL volume for 20 minutes. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pone.0240169. For example, efficacy, pharmacokinetics, clinical pathology, toxicity endpoints, systemic exposure, and biomarker endpoints can all be collected from one animal at several timepoints. 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. Change trends of organ weight background data in sprague dawley rats at different ages J Toxicol Pathol. 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. Discover a faster, simpler path to publishing in a high-quality journal. 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. K) Images of wild-type Sprague Dawley and SRG rat spleen. Writing – original draft. L) Quantitative comparison of wild-type Sprague Dawley versus SRG spleen and thymus at 8 weeks of age. The rats … Taken together, SRG rats are a valuable addition to the existing mouse models for use in preclinical oncology research. To determine if the SRG rats supports the growth of human xenografts, we inoculated several human cancer cell lines known to grow in immunodeficient mouse models. Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Affiliation In 1991, 8 colonies were selected to form the IGS Foundation Colony. D-F) CD45R (B220)+/IgM+ cells in D) wild-type spleen and E) the SRG spleen. 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 ®). 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. Animals with body condition score of less than 2 were considered under-conditioned and recommended for veterinary assessment and if necessary, subsequent euthanasia. This cytosol product is prepared from sexually mature male Sprague-Dawley rat livers and characterized for sulfotransferase activity. Furthermore, the rat can humanely support the growth of tumors that are 10 times the size of those in the mouse, which allows for more tissue at study completion for downstream analyses. 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]. Our goal is the ultimate translation of these capabilities into the clinic. R. W. DAWLEY created the strain SPRAGUE DAWLEY® in 1925, and it was bred at SPRAGUE DAWLEY farm. J) Image of wild-type Sprague Dawley versus SRG thymus. Thirty four SRG rats were used for PDX establishment studies and thirty four SRG rats were engrafted with commercially available cell lines for xenograft development. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. The SRG rat supports the growth of multiple human cancer cell lines, including lines that do not engraft or grow well in existing mouse models, such as VCaP. (Unpaired t-test, p-values: * < 0.05). 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. Investigation, These rats typically have increased tail to body length ratio compared with Wistar rats. C) Western blotting for AR in tumor tissue from the SRG rat. Citation: Noto FK, Sangodkar J, Adedeji BT, Moody S, McClain CB, Tong M, et al. *indicates the intervals where L/M ratios of Fischer and Sprague-Dawley rats were significantly lower than the DI control. [5] This breed of rat was first produced by the Sprague Dawley farms in Madison, Wisconsin (later to become the Sprague Dawley Animal Company). "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. Serum PSA analysis was not performed for SCID/NCr mice since the procedure would require a terminal blood draw due to the much lower blood volume in the mice. 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]. Animals were treated with an analgesic (carprofen 5 mg/kg subcutaneously) immediately post-surgery. Tumor growth was monitored by externally measuring the greatest longtitudinal diameter (length) and the greatest transverse diameter (width) using digital calipers (Fowler #54-100-067-1) 3 times a week. Our recent study is the first study that demonstrated the presence of tyrosine phosphorylated proteins in epithelium and fluid of epididymis of Sprague-Dawley rats.Herein, we showed for the first time that tyrosine phosphorylated proteins were expressed in adult rat epididymal epithelium specifically in cytoplasm of principle cells, nuclei of apical cells and basal cells (Fig. ¶‡ GN and TYJ also contributed equally to this work. Poseida Therapeutics Inc., San Diego, California, United States of America, Affiliation This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley … Analgesics (meloxicam or carprofen) are administered as needed to manage suspected pain. The SRG rat is completely devoid of circulating mature B cells (G) compared to wild-type (F). De-identified patient samples were provided to Hera Biolabs in DMEM + 10% FBS, 1% Penicillin/Streptomycin, 1% Amphotericin B. studied the development of the hair follicle in individuals that displayed the hairless phenotype. Effects of genistein on male sprague dawley rats reproductive development. 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. The wild-type Sprague Dawley rat thymus was comprised mostly of CD4/CD8 double positive cells whereas in the SRG rat, the viable cells recovered were CD4-/CD8- (Fig 1A–1C). Serum was analyzed for PSA by ELISA (ALPCO #25-PSAHU-E01) according to manufacturer’s instructions. Immunodeficient mice have proven essential for the establishment of in vivo human tumor models. 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. Division of Genetic Medicine, Department of Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles Molecular characterization and histological analyses were performed for three PDX lines and showed high concordance between passages 1, 2 and 3 (P1, P2, P3), and the original patient sample. 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. Even if successfully engrafted and established, multiple passages in the mouse are required to generate enough tissue for efficacy studies due to the small tumor volume supported by the mouse, which makes it technically very challenging to generate personalized drug-response data in a timely manner to affect patient treatment. 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 No, Is the Subject Area "Malignant tumors" applicable to this article? In order to Formal analysis, 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). Animals are euthanized if tumors grow to longer than 40 in diameter on the longest edge, or when they reach 10% of the body weight (e.g. C) Quantification of data, n = 3, error ± SD. Its main advantage is its calmness and ease of handling. 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). Originated in 1925 by Robert W. Dawley from a hybrid hooded male and a female Wistar rat. When your research demands versatility and consistency, turn to the Sprague Several strategies have been utilized to develop genomic alterations in rats [12–14]. SDR rats demonstrated high efficiency and desirable uniformity in a variety of human tumor growth profiles and grew tumors to nearly ten times the volume (or double the diameter) allowed in mice. Sprague Dawley rat: The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Then, sampling was done from rats … Overall, SRG rats demonstrated favorable take rate and growth kinetics for downstream efficacy studies. Taconic’s proven process ensures timed-pregnant rats bear litters within a 24-hour window of your desired gestational age. Immediately prior to injection, 250 μL 10 mg/mL Cultrex BME3 (Trevigen #3632-001-02) or Matrigel (Corning #354234) was added to the cell suspension for a final Cultrex or Matrigel concentration of 5 mg/mL. Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. Our analysis evaluated the variants detected within NSCLC-related genes such as KRAS, RAS, EGFR, and MET. SD rats are docile and are easy to handle. These include cell lines that have poor take rates or variable growth kinetics in mice. Formal analysis, The caveat to using the rat for efficacy studies is the need for larger amounts of dosing materials. Yes By having this kind of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude variations in genetics as a factor. The Sprague Dawley rat was first produced at Sprague Dawley farms, now a corporation called Harlan Sprague Dawley, and is widely used due in part to its calmness and ability to be handled easily. Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan, United States of America, C-E) Quantification of data T cell populations, n = 3, error ±SD. Subsequent passages from mouse/rat to mouse/rat are annotated as PDX passage 2, 3 or P2, P3, etc, to establish a bank of tissues. Surgically resected NSCLC tissue from nine patients were obtained from the Biospecimen Procurement and Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558) in collaboration with Dr. Mark Evers under an approved University of Kentucky IRB application. Click through the PLOS taxonomy to find articles in your field. The excellent reproductive performance of the Sprague Dawley model makes it a preferred choice for generating timed- pregnant females. The ability to transfer and propagate human tumors in animal models allows for unique opportunities to study tumor biology, dissect the molecular mechanisms driving tumor development and progression, and evaluate treatment response. 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]. Writing – original draft, Affiliation CD® (Sprague Dawley) IGS Rat Details. VCaP cells are difficult to maintain in vitro and display variable growth kinetics in vivo between published research groups [16]. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. 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. Yes 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. Tumors were placed on the dorsal side of the flank so that they did not interfere with normal mobility or ability to nest properly. https://doi.org/10.1371/journal.pone.0240169.t002. This does not alter our adherence to PLOS ONE policies on sharing data and materials. D) Tumor growth curve in SRG rats inoculated with 10 x106 786-O cells. https://doi.org/10.1371/journal.pone.0240169.g002. If analgesics do not relieve pain as measured by clinical criteria mentioned above, the animal is euthanized. SAS Sprague Dawley Rat Details. In vivo models are essential in determining the effectiveness and safety of potential treatments prior to clinical testing in patients. for a 200 g animal, the tumor cannot weigh more than 20 g = 20,000 mm3). The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. Pilot studies demonstrated that SRG rats had an 80% take rate. Authors Ying Piao 1 , Yunen Liu, Xiaodong Xie. (Unpaired t-test, p-values: * < 0.05). Our data suggest the SRG OncoRat is a valuable tool for establishing PDX banks and thus serves as an alternative to current PDX mouse models hindered by low engraftment rates, slow tumor growth kinetics, and multiple passages to develop adequate tissue banks. e0240169. We further demonstrated that SRG rats have high engraftment rates, favorable growth kinetics for efficacy studies, and can support … In rats, this is accomplished through inbreeding. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. No, Is the Subject Area "Spleen" applicable to this article? Copyright: © 2020 Noto et al. Splenocytes, thymocytes, and whole blood were collected from wild-type and SRG rats and analyzed by flow cytometry to characterize the immune cell populations. 2013 Mar;26(1):29-34. doi: 10.1293/tox.26.29. Our data also demonstrate SRG rats support PDX engraftment and may accelerate the timeframe for PDX propagation and preclinical efficacy studies. 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. (Unpaired t-test, p-values: * < 0.05). In addition, SRG rats are highly permissive to engraftment with NSCLC-PDX tumors from patients. LNCaP/AR cells were a kind gift from Dr. Charles Sawyers (Memorial Sloan Kettering Cancer Center, New York, NY). This in turn results in PDXs that no longer faithfully reflect the genomic landscape of the primary tumors. Rats also accommodate serial blood and tumor tissue sampling for temporal assessment of several parameters from the same animal. 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. Footshock could be avoided by pressing a lever during a danger period prior to onset of shock. For more information about PLOS Subject Areas, click https://doi.org/10.1371/journal.pone.0240169.g003. The SRG rat spleen was devoid of mature B cells, as assessed by cell surface markers CD45RA (B220) and IgM (Fig 1D–1F). 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. 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