Data were collected from 40 Wistar-Kyoto (WKY) and 40 Sprague Dawley (SD) rats during an active escape-avoidance experiment. Serum was analyzed for PSA by ELISA (ALPCO #25-PSAHU-E01) according to manufacturer’s instructions. "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. Blood was collected in K2EDTA tubes. Formal analysis, 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. P<0.05 was considered statistically significant. 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. Methodology, Writing – original draft, Affiliation In 1991, 8 colonies were selected to form the IGS Foundation Colony. Sprague-Dawley rats were anesthetized and exposed to saline or nicotine aerosol for 15 min and transferred to room air. This in turn results in PDXs that no longer faithfully reflect the genomic landscape of the primary tumors. The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. 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. 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. Rederived into an isolator foundation colony in 1997. These rats typically have increased tail to body length ratio compared with Wistar rats. 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 … Immunohistochemical analyses were used to further confirm the prostatic origin of these tumors. The average litter size of the Sprague Dawley rat is 10.5. Sudeh Izadmehr acknowledges support from the National Institues of Health Loan Repayment Program. D) Compilation of PSA in the serum of SRG rat inoculated with VCaP cells correlates with tumor volume. 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). Writing – original draft, Affiliation e0240169. 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. 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. 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 … 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). Yes Genetic analyses were performed for three of the PDX lines at multiple passages for each line in addition to the original patient sample. C) Western blotting for AR in tumor tissue from the SRG rat. 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. If analgesics do not relieve pain as measured by clinical criteria mentioned above, the animal is euthanized. https://doi.org/10.1371/journal.pone.0240169.s001, https://doi.org/10.1371/journal.pone.0240169.s002. 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. 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. One of the most robust and well characterized mouse models is the non-obese diabetic (NOD) Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG mouse). R. W. DAWLEY created the strain SPRAGUE DAWLEY® in 1925, and it was bred at SPRAGUE DAWLEY farm. 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. 2013 Mar;26(1):29-34. doi: 10.1293/tox.26.29. 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 … 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. Funding: NCI contract HHSN261201700017C supported PDX establishment and their molecular and histological characterizations, along with their drug response studies. CropLife International fully acknowledges the source and authors of the publication as detailed above. Sprague Dawley rat: The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical and nutritional research. One such cell line is VCaP, a human prostate cancer cell line derived from a vertebral metastatic growth. (Unpaired t-test, p-values: **** < 0.0001). Jaya Sangodkar, Roles 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. Division of Genetic Medicine, Department of Medicine, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles 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. Immunodeficient mice have proven essential for the establishment of in vivo human tumor models. Department of Obstetrics and Gynecology, The University of Michigan, Ann Arbor, Michigan, United States of America, Roles The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan … Its main advantage is its calmness and ease of handling. Growth kinetics of these human cancer cell lines have been tested by others in mouse xenograft models [21–24]. The lack of thymus tissue in the SRG rat results in a low recovery of viable thymocytes. [25] Cells were resuspended in 250 μL of each cell line’s respective culture media as listed in the Cell Culture methods. Taken together, SRG rats are a valuable addition to the existing mouse models for use in preclinical oncology research. Then, sampling was done from rats … J) Image of wild-type Sprague Dawley versus SRG thymus. Compared to mice, rats are bigger, generally more aggressive, and more resistant to various ailments. 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. 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 … 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. To detect T, B, and NK cells in SRG rats, flow cytometric analysis was performed on splenocyte, thymocytes, and whole peripheral blood using a BD LSRII. 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]. No, Is the Subject Area "Mouse models" applicable to this article? Hera BioLabs Inc., Lexington, Kentucky, United States of America, 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). Sample 3067 (C) was implanted into SRG rats for P1 and then serially implanted into NSG mice for P2 and P3. 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). Investigation, Affiliation To Charles River in 1950 from Sprague Dawley, Inc. 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. 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®). All cell lines were originally purchased from ATCC. G-I) NK cells in G) wild-type rat spleen and H) SRG rat spleen. 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. A) Tumor growth curve shows multiple passages of the patient derived lung tumor from one patient and subsequent passages in the SRG rat. LNCaP/AR cells were a kind gift from Dr. Charles Sawyers (Memorial Sloan Kettering Cancer Center, New York, NY). Litter average: 11.0. Yes Tissue were stained for H&E by IDEXX or Icahn School of Medicine at Mount Sinai Pathology Core Facility. 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). Here we highlight growth kinetics of several human cancer cell lines and NSCLC-PDX samples in the SRG rat. F) Quantification of data, n = 3, error ± SD. We investigated the possible protective effects of lycopene and curcumin on the parotid glands of 40 female Sprague Dawley rats during irradiation. Yes Authors Ying Piao 1 , Yunen Liu, Xiaodong Xie. 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. For tissue expansion, PDX tumors were excised from animals aseptically, sectioned into 2mm x 2mm pieces, and implanted into SRG rats and into NSG mice, using the same method. Data is presented as mean ± standard deviation or mean ± standard error of the mean as noted in the figures. 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. Formal analysis, Analgesics (meloxicam or carprofen) are administered as needed to manage suspected pain. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, United States of America, If an animal loses greater than 20% initial body weight, they are euthanized. To Charles River in 1996. Tumors were placed on the dorsal side of the flank so that they did not interfere with normal mobility or ability to nest properly. We next determined if SRG rats support the growth of human cancer cell lines that are difficult to grow in immunodeficient mouse strains. Individual level tumor measurements and body-weight data for all xenografts are provided in the supplemental tables. 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. 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. 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. Animal technicians are trained through AALAS courses, including “Post-Procedural Care of Mice and Rats in Research; Minimimzing Pain and Distress”. A-E) T cells in peripheral blood in A) wild-type rat and B) SRG rat. Data represent average of 3 from each strain with SEM (Unpaired t-test, p-values: **** < 0.0001). Originated in 1925 by Robert W. Dawley from a hybrid hooded male and a female Wistar rat. 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. Its main advantage is its calmness and ease of handling. Conceptualization, This model has been tested and validated for use in oncology (SRG OncoRat®). The Il2rg knockout in the SRG rat results in significantly fewer NK cells than the single Rag2 knockout rat [8]. SAS Sprague Dawley Rat Details. No, Is the Subject Area "NK cells" applicable to this article? There were no changes observed in motility or food intake in tumor bearing animals. Data Availability: All relevant data are within the paper and its Supporting Information files. However, characteristic of the species, the rat will still use its sharp incisors to bite if it is handled improperly. Our analysis evaluated the variants detected within NSCLC-related genes such as KRAS, RAS, EGFR, and MET. All the cells were grown in a humidified incubator at 37°C with 5% CO2. H) Quantification of data, n = 3, error ± SD. The SRG rat spleen also has lower NK cells compared to the wild-type rat spleen (6.11%± 1.98 vs. 1.31% ± 1.31, respectively; Fig 1G–1I). 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