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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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            The cotton rat model of respiratory viral infections.

            Development of successful vaccines against human infectious diseases depends on using appropriate animal models for testing vaccine efficacy and safety. For some viral infections the task is further complicated by the frequently changing genetic make-up of the virus, as in the case of influenza, or by the existence of the little-understood phenomenon of vaccine-enhanced disease, as in the case of respiratory syncytial virus (RSV). The cotton rat Sigmodon hispidus has been used for years as an excellent small animal model of the RSV vaccine-enhanced disease. Recently, using cotton rats, we have demonstrated that vaccination against another paramyxovirus, human metapneumovirus (hMPV), can also lead to vaccine-enhanced disease. In addition to the study of paramyxoviruses, S. hispidus presents important advantages for the study of orthomyxoviruses such as influenza. The cotton rat is susceptible to infection with unadapted human influenza strains, and heterosubtypic immunity to influenza can be evoked in S. hispidus. The mechanisms of influenza, RSV, and hMPV pathogenesis and immunity can now be investigated in the cotton rat with the development of species-specific reagents for this animal model.
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              The cotton rat (Sigmodon hispidus) is a permissive small animal model of human metapneumovirus infection, pathogenesis, and protective immunity.

              Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 x 10(2) PFU/gram tissue (C3H mice) to greater than 10(5) PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 x 10(5) PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.
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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
                07e3732e-96fa-4b74-9d07-b65a2689998d
                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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                cotton rat,research animal model,human diseases,immunology,polio,typhus,husbandry

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