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      Cotton Rat

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          This chapter studies the cotton rat, Sigmodon hispidus, which is a New World rodent with a stocky, robust stature. The average adult weight of a cotton rat is between 100 and 250 gm. The name Sigmodon comes from the sigmoid enamel loops on the grinding surface of the molar. Sexual dimorphism is not prominent, but males and females can be distinguished based on the size of the genital papilla and distance from the anus. The cotton rat is distinguished from the Norway rat by its smaller size, shorter tail, and longer grizzled fur. The lifespan of the hispid cotton rat is less than 6 months in the wild but in captivity animals have a survival span up to 23 months of age. The cotton rat ( Sigmodon) species has been recognized as a significant animal model for diseases caused by a variety of human and rodent pathogens. The primary research use for cotton rats is for studies into infectious disease and immunology.

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          The cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis.

          Influenza A virus continues to cause annual epidemics. The emergence of avian viruses in the human population poses a pandemic threat, and has highlighted the need for more effective influenza vaccines and antivirals. Development of such therapeutics would be enhanced by the use of a small-animal model that is permissive for replication of human influenza virus, and for which reagents are available to dissect the host response. A model is presented of nasal and pulmonary infection in adult inbred cotton rats (Sigmodon hispidus) that does not require viral 'adaptation'. It was previously demonstrated that animals infected intranasally with 10(7) TCID50 of a recent H3N2 influenza, A/Wuhan/359/95, have increased breathing rates. In this report it is shown that this is accompanied by weight loss and decreased temperature. Virus replication peaked within 24 h in the lung, with peak titres proportional to the infecting dose, clearing by day 3. Replication was more permissive in nasal tissues, and persisted for 6 days. Pulmonary pathology included early bronchiolar epithelial cell damage, followed by extensive alveolar and interstitial pneumonia, which persisted for nearly 3 weeks. Interleukin 1 alpha (IL1alpha), alpha interferon (IFN-alpha), IL6, tumour necrosis factor alpha (TNF-alpha), GROalpha and MIP-1beta mRNA were elevated soon after infection, and expression coincided with virus replication. A biphasic response was observed for RANTES, IFN-gamma, IL4, IL10 and IL12-p40, with increased mRNA levels early during virus replication followed by a later increase that coincided with pulmonary inflammation. These results indicate that cotton rats will be useful for further studies of influenza pathogenesis and immunity.
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            Diversifying animal models: the use of hispid cotton rats (Sigmodon hispidus) in infectious diseases.

            The hispid cotton rat (Sigmodon hispidus) has been a longstanding laboratory animal model of infectious diseases. In this review, the most common usage of hispid cotton rats as models of infectious diseases is discussed in detail and all organisms, which have been shown to infect cotton rats, are listed. A state of the art overview is given on handling and maintenance of hispid cotton rats as well as experimental techniques such as narcosis and blood withdrawal. Most importantly, through the development of new reagents, the hispid cotton rat can be used to study immune responses against the respective pathogen. Hispid cotton rat cytokine and chemokine genes have been sequenced and cotton rat specific antibodies and cell lines have been produced which in connection with the establishment of immunological methods should facilitate the use of hispid cotton rats as animal models in the pathogenesis of infectious diseases.
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              Lysostaphin cream eradicates Staphylococcus aureus nasal colonization in a cotton rat model.

              The anterior nares are a primary ecologic niche for Staphylococcus aureus, and nasal colonization by this opportunistic pathogen increases the risk of development of S. aureus infection. Clearance of S. aureus nasal colonization greatly reduces this risk. Mupirocin ointment is the current standard of care for clearance of S. aureus nasal colonization, but resistance to this antibiotic is emerging. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the cross-linking pentaglycine bridges in the cell walls of staphylococci. Lysostaphin is extremely staphylocidal (MIC at which 90% of isolates are inhibited, 0.001 to 0.064 micro g/ml) and rapidly lyses both actively growing and quiescent S. aureus. This study demonstrates that a single application of 0.5% lysostaphin (actual dose, approximately 150 micro g of lysostaphin), formulated in a petrolatum-based cream, dramatically reduces S. aureus nasal colonization in 100% of animals tested and eradicates S. aureus nasal colonization in 93% of animals in a cotton rat model. A single dose of lysostaphin cream is more effective than a single dose of mupirocin ointment in eradicating S. aureus nasal colonization in this animal model. The lantibiotic peptide nisin, which has potent in vitro antistaphylococcal activity, was ineffective in reducing staphylococcal nasal carriage in this model. Nasal colonization was not reduced after three treatments with 5% nisin ( approximately 1,500 micro g/dose) in any of the treated animals. Lysostaphin formulated in cream may prove to be a superior alternative to mupirocin ointment for clearance of S. aureus nasal colonization.
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                Author and article information

                Journal
                The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents
                The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents
                16 December 2011
                2012
                16 December 2011
                : 1105-1113
                Affiliations
                Harlan Laboratories, Inc., Indianapolis, IN, USA
                Article
                B978-0-12-380920-9.00049-3
                10.1016/B978-0-12-380920-9.00049-3
                7150299
                Copyright © 2012 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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