Studies were conducted after Institutional Animal Care and Use Committee approval and in strict compliance with institutional regulatory standards and guidelines. 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]. All the cells were grown in a humidified incubator at 37°C with 5% CO2. 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. Oral Administration of Aloe vera Ameliorates Wound Healing through Improved Angiogenesis and chemotaxis in Sprague Dawley Rats (E-pub Ahead of Print) While patient derived xenograft (PDX) models are a valuable cancer model, there are some limitations in employing such model systems for precision medicine approaches. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. 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. here. Healthy Sprague–Dawley (SD) rats were given black tea for 4 weeks, and cecum content, serum, intestinal, and hepatic samples were collected. Taken together, SRG rats are a valuable addition to the existing mouse models for use in preclinical oncology research. This model has been tested and validated for use in oncology (SRG OncoRat®) with different human cancer cell lines and PDXs. (2020) The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. Our data also demonstrate SRG rats support PDX engraftment and may accelerate the timeframe for PDX propagation and preclinical efficacy studies. Tumor diameter was measured using digital calipers 3 times a week. The first Sprague Dawley® rat colony began in 1925, when Robert Dawley developed a vigorous rat with a good temperament and high rates of lactation. studied the development of the hair follicle in individuals that displayed the hairless phenotype. DAB substrate was applied followed by counterstaining with hematoxylin. Analgesics (meloxicam or carprofen) are administered as needed to manage suspected pain. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. Fallon K. Noto, 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). (Unpaired t-test, p-values: ** < 0.01). Tissues were stained with H&E, P40, and TTF1. PLoS ONE 15(10): Another rodent, the rat (Rattus norvegicus), is the second most cited animal model used in biomedical research. A hot aqueous 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. The SRG rat also carries a 16bp deletion in the first exon of the Il2rg gene to knock out its function. Formal analysis, Its main advantage is its calmness and ease of handling. In 1991, 8 colonies were selected to form the IGS Foundation Colony. To SASCO from ARS/Sprague Dawley in 1979. Several strategies have been utilized to develop genomic alterations in rats [12–14]. Sprague-Dawley rats (male 250–350 g, Taconic Farms) are anesthetized with chloral hydrate (400 mg/kg, i.p.) SAS Sprague Dawley Rat Details. We investigated the possible protective effects of lycopene and curcumin on the parotid glands of 40 female Sprague Dawley rats during irradiation. Each graph depicts tumor volumes for individual animals for 6 different NSCLC patient samples (A-F). 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). 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. PDF | Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. 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 rat is the most commonly used rodent species for toxicology studies. [1][2][3][4] Its main advantage is its calmness and ease of handling. Is the Subject Area "Prostate cancer" applicable to this article? "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. Our studies have demonstrated that SRG rats support growth of a wide array of human cancer cell lines, including ones that have poor uptake or variable growth kinetics in available mouse models. The suspension of cells and Cultrex/Matrigel was injected subcutaneously into the hindflank. 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 … Goat anti-mouse IgG-HRP conjugate antibody (PI31430, ThermoFisher Scientific) or Goat anti-rabbit IgG-HRP conjugate antibody (31460, ThermoFisher Scientific) were used as secondary antibodies. All cell lines were originally purchased from ATCC. Growth kinetics of these human cancer cell lines have been tested by others in mouse xenograft models [21–24]. 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). 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). Then, sampling was done from rats … The Il2rg knockout in the SRG rat results in significantly fewer NK cells than the single Rag2 knockout rat [8]. If avoidance did not occur, a series of footshocks was administered, and the rat could press a lever to escape (terminate shocks). This is in contrast to the SDR (Rag2 single knockout) rat, which has highly elevated NK cells compared to the wild-type rat [15]. For more information about PLOS Subject Areas, click Case Western Reserve University, Cleveland, Ohio, United States of America, Affiliation One of the most robust and well characterized mouse models is the non-obese diabetic (NOD) Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG mouse). In 1991, 8 colonies were selected to form the IGS Foundation Colony. 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. The study followed European Union regulations 86/609/EEC, 2010/63/EU for … "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. 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. 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. CD4+/CD8+ mature T cells are absent from SRG thymocytes, compared to a wild-type control. Seven SCID/NCr (CB17/Icr-Prkdcscid/IcrCr) male mice (BALB/c background, strain 01S11, The NCI Animal Production Program, Frederick, MD) were used for VCaP xenograft mouse study. The average litter size of the Sprague Dawley rat is 10.5. The lack of thymus tissue in the SRG rat results in a low recovery of viable thymocytes. We further demonstrated that SRG rats have high engraftment rates, favorable growth kinetics for efficacy studies, and can support … 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 https://doi.org/10.1371/journal.pone.0240169.t001. If analgesics do not relieve pain as measured by clinical criteria mentioned above, the animal is euthanized. The SRG rats have a smaller spleen compared to wild-type Sprague Dawley rats and are essentially athymic (Fig 1J–1L), resulting in low viable cell yield from the thymus. 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). This is the first study to document the positive effect of a wild blueberry-enriched diet on the composition and structure of the extra-cellular matrix of Sprague-Dawley rat aortas, which may result in lower binding of the LDL particle on the arterial wall, reducing the risk from atherosclerosis," said Dr. Yes In SCID/NCr mice, VCaP tumors engrafted in 60% of the mice but the growth kinetics were highly variable. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Authors Ying Piao 1 , Yunen Liu, Xiaodong Xie. Sample 3067 (C) was implanted into SRG rats for P1 and then serially implanted into NSG mice for P2 and P3. The chart below indicates specific parameters that are monitored (Table 1). 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. A : schematic representation of our exposure paradigm. Blood was collected from SRG rats in Clot activator SST microtainers prior to inoculation of VCaP cells and then weekly throughout the study. METHODS: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Laboratory rats such as the Sprague-Dawley (SD) rats are an important model for biomedical studies in relation to human physiological or pathogenic processes. R. W. DAWLEY created the strain SPRAGUE DAWLEY® in 1925, and it was bred at SPRAGUE DAWLEY farm. 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. The hairless mutation appeared in a SPRAGUE DAWLEY® colony in 2004; Bazzi et al. Sprague-Dawley rats were anesthetized and exposed to saline or nicotine aerosol for 15 min and transferred to room air. 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. Formal analysis, 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). 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). 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. No, Is the Subject Area "Colorectal cancer" applicable to this article? Sprague-Dawley and Wistar are the two most frequently used rat models. Division of Genetic Medicine, Department of Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles Weight and tumor measurements (length and volume) were recorded 3 times weekly on Monday, Wednesday, and Friday. Index, The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. Click through the PLOS taxonomy to find articles in your field. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. In addition to the colorectal cell line HCT-116, we also assessed the growth of several other cell lines in SRG rats (Fig 3B–3D): pancreatic cancer cell line MIA-PaCa-2, breast cancer cell line HCC1954, and renal cancer cell line 786-O. A) Tumor growth curve in NSG mice and SRG rats inoculated with 2x106 HCT-116 cells subcutaneously in the hind flank. Sudeh Izadmehr acknowledges support from the National Institues of Health Loan Repayment Program. A-C) CD4+/CD8+ mature T cells in A) wild type control and B) SRG rat thymocytes. 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+). 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. Animals were treated with an analgesic (carprofen 5 mg/kg subcutaneously) immediately post-surgery. Effects of genistein on male sprague dawley rats reproductive development. Splenocytes, thymocytes, and whole blood were collected from wild-type and SRG rats and analyzed by flow cytometry to characterize the immune cell populations. 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). https://doi.org/10.1371/journal.pone.0240169.g001. These measurements and all health observations were performed by trained animal care technicians and referred to veterinary staff if abnormalities were observed. Tumor width and length were measured three times weekly to calculate volume. For all staining, tissue slides were incubated with primary antibody overnight at 4°C. 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). 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. Other aspects of health were evaluated, such as body weight (20% body weight loss at any time point warrants euthanasia), body condition score, tumor ulceration, and ensuring that the tumor does not interfere with locomotion or normal activities. Hera BioLabs Inc., Lexington, Kentucky, United States of America, Roles 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. 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. Genetic analyses were performed for three of the PDX lines at multiple passages for each line in addition to the original patient sample. Graphpad Prism 7 was used to perform all statistical analyses. SD rats have a white coat color (albino). https://doi.org/10.1371/journal.pone.0240169.s001, https://doi.org/10.1371/journal.pone.0240169.s002. 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. A strain, in reference to rodents, is a group in which all members are, as nearly as possible, genetically identical. 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. Rats were . 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. 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. METHODS: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. [25] I-K) NK cells in the I) wild-type rat (10.1% CD161a+) and J) SRG rat (0.5% CD161a+). 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). This in turn results in PDXs that no longer faithfully reflect the genomic landscape of the primary tumors. Euthanasia may also be carried out if the above are not met but the animal has reduced body condition score, hunched posture, ungroomed fur, porphyrin, respiratory abnormalities, impaired mobility or ability to perform daily tasks (eating, sleeping, ambulating) due to the position or size of the tumor, or unalleviated pain as suggested by the grimace scale and vocalization upon handling. P1 is the initial passage in vivo in SRG rats. 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. In rats, this is accomplished through inbreeding. 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. CD® (Sprague Dawley) IGS Rat Details. The Hsd:Sprague Dawley ® SD rat has a wide array of historical research use including in the field of cardiology. 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 … 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). These include cell lines that have poor take rates or variable growth kinetics in mice. Goutham Narla is on the scientific advisory board for Hera Biolabs in DMEM + 10 % FBS, %! 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Is on the scientific advisory board for Hera Biolabs in DMEM + 10 % FBS, 1 Amphotericin. And volume ) were recorded 3 times a week tumor growth curve SRG... 4 ] its main advantage is its calmness and ease of handling tissue were stained H. The timeframe for PDX establishment studies of viable thymocytes lung tumor from one patient and subsequent passages in the of... % initial body weight is 250-300g for females, and Friday and exposed to saline or nicotine for...

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