Cotton Rats Sigmodon Hispidus Research Articles

Genetic and Conservation Status of a Relictual Population of the Hispid Cotton Rat (Sigmodon hispidus eremicus)

Abstract DNA sequences from the mitochondrial cytochrome-b gene were examined in individuals of the hispid cotton rat (Sigmodon hispidus eremicus) collected from an isolated population in southwestern Arizona. Analyses indicated unique DNA substitutions and haplotypes that were restricted to the population in Arizona and an overall genetic affiliation to populations of the western lineage of S. hispidus, particularly to the population from Otero County, New Mexico. Estimates of time since divergence indicated an allopatric relationship with other populations of S. hispidus ≥150,000 years ago. Additionally, data obtained from analyses of amplified fragment-length polymorphisms indicated that S. h. eremicus exhibits lower genetic diversity compared to other populations. Together, these data along with detection of two replacements of apomorphic nonsynonymous amino acids and genetic divergence among amplified length polymorphisms argue that S. h. eremicus is unique from other populations of S. hispidus and t...

Efficacy of trivalent inactivated influenza vaccines in the cotton rat Sigmodon hispidus model

Annually adjusted inactivated influenza vaccines can prevent infection and limit the spread of seasonal influenza when vaccine strain closely matches circulating strain. For the years when the match is difficult to achieve, a rapid screening of a larger repertoire of vaccines may be required but is difficult to accomplish due to the lack of a convenient small animal model of seasonal influenza vaccines. The goal of this work was to determine whether the cotton rat Sigmodon hispidus, a small laboratory animal susceptible to infection with unadapted influenza viruses, may become such a model. Cotton rats were immunized with a trivalent inactivated vaccine (TIV) FluLaval (2006/2007) and vaccine immunogenicity and antiviral efficacy was evaluated against the homologous H1N1 and a heterologous H3N2 challenge. FluLaval induced a strong virus-specific IgG and neutralizing antibody response against homologous virus, elicited sterilizing immunity in the lungs and significantly reduced viral replication in the nose of infected animals. FluLaval was efficacious in cotton rats as either a single-time or a double immunization, although higher level of protection of the upper respiratory tract was achieved following two doses of vaccine. Antibodies against a heterologous influenza strain were induced in FluLaval-vaccinated animals, but vaccine lacked antiviral efficacy and did not reduce replication of a heterologous virus. Similarity of these findings to human TIV data suggests that the cotton rat may prove to be a reliable small animal model of human influenza vaccines.

Responses of Small Mammals and Vegetation to a Prescribed Burn in a Tallgrass Blackland Prairie

Abstract This study investigated effects of a prescribed burn on the small mammal community and vegetative cover in a tallgrass prairie remnant in east central Texas. Small mammals were live-trapped 8 mo before and 8 mo after a prescribed burn. Vegetation sampling confirmed drastic reduction of cover after fire in the grassland sections of the prairie. Relative abundances (captures/100 trapnights) of pygmy mice (Baiomys taylori) and cotton rats (Sigmodon hispidus) significantly decreased after the fire, whereas deer mice (Peromyscus maniculatus) significantly increased following fire. Cotton rat and pygmy mouse abundances were positively correlated with grassy litter and negatively correlated with bare ground, whereas deer mouse abundance was positively correlated with bare ground. Relative abundances of B. taylori, S. hispidus and P. maniculatus in burned sections returned to preburn levels in 8 mo. Hispid pocket mice (Chaetodipus hispidus) were not captured until after the prescribed burn. This is the f...

Light and transmission electron microscopic characteristics of a novel Hepatozoon spp. in naturally infected cotton rats (Sigmodon hispidus)

A novel species of Hepatozoon was recently reported in cotton rats (Sigmodon hispidus) collected from an area of Oklahoma where American canine hepatozoonosis is endemic. In this study, the various stages of merogony of the parasite were characterized by light and electron microscopy. Meronts occurred within parasitophorous vacuoles in hepatocytes and ranged from mononucleated spherical forms to large, mature forms in vacuoles that contained approximately 50 peripherally arranged merozoites. Developing merozoites had characteristic apicomplexan organelles, including anterior and posterior polar rings, a conoid, microtubules, rhoptries, micronemes, and a trilaminar membrane. As the meronts matured, numerous curvilinear merozoites budded from a residual body. This morphologic characterization extends our understanding of this novel Hepatozoon and adds information about the hepatozoa, apicomplexan parasites that infect numerous species.

Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

BackgroundIncreased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.MethodsLung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.ResultsAdult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to Penh were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in Penh in infant animals.ConclusionWhile respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.

Environmental Correlates of Survival and Reproduction in Old-Field Rodents

We used regression trees to assess seasonal relationships between vital rates (survival and reproduction) and a suite of environmental variables for hispid cotton rats (Sigmodon hispidus) and prairie voles (Microtus ochrogaster). We found only 2 relationships between vital rates and environmental variables for M. ochrogaster, whereas we found relationships in all seasons for S. hispidus. The majority of recovered regression trees contained multiple variables, indicating that the vital rates of S. hispidus were affected by interactions among environmental correlates. Vital rates of S. hispidus were affected most by precipitation, temperature, and snowfall; but the direction of effects of these environmental variables was not consistent among seasons. Our analyses indicate that populations of M. ochrogaster in northeastern Kansas are relatively insensitive to environmental variability, whereas survival and reproduction in S. hispidus are influenced by the environment throughout the year.

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.

Testing the Limits of Rodent Sperm Analysis: Azoospermia in an Otherwise Healthy Wild Rodent Population

By comparing the sperm parameters of small rodents trapped at contaminated terrestrial sites and nearby habitat-matched noncontaminated locations, the patent-pending Rodent Sperm Analysis (RSA) method provides a direct health status appraisal for the maximally chemical-exposed mammalian ecological receptor in the wild. RSA outcomes have consistently allowed for as definitive determinations of receptor health as are possible at the present time, thereby streamlining the ecological risk assessment (ERA) process. Here, we describe the unanticipated discovery, at a contaminated US EPA Superfund National Priorities List site, of a population of Hispid cotton rats (Sigmodon hispidus), with a high percentage of adult males lacking sperm entirely (azoospermia). In light of the RSA method's role in streamlining ERAs and in bringing contaminated Superfund-type site investigations to closure, we consider the consequences of the discovery. The two matters specifically discussed are (1) the computation of a population's average sperm count where azoospermia is present and (2) the merits of the RSA method and its sperm parameter thresholds-for-effect when azoospermia is masked in an otherwise apparently healthy rodent population.

Comment on: Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland

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Respiratory syncytial virus replication is prolonged by a concomitant allergic response

Epidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported. Cotton rats (Sigmodon hispidus) that have been used as a model to study RSV pathogenesis were sensitized to extracts of Aspergillus fumigatus (Af), a common household mould. The allergic response to Af included eosinophilia, formation of granulomas and induction of Th2 type cytokines. RSV infection prior to allergen challenge resulted in exacerbation of the inflammatory response as well as increased airway responsiveness to methacholine. The exacerbated response was indeed dependent on virus replication. Virus replication in turn was influenced by the allergic response, with persistence in the noses for 2 days longer in animals challenged with allergen. This diminished clearance corresponded to decreased induction of mRNA for IFN-gamma, a Th1-type cytokine that is characteristic of viral infection. Treatment of RSV-infected Af-challenged animals with recombinant IFN-gamma reduced the allergic inflammatory response as well as the relative levels of Th1 and Th2 cytokine mRNA. However, this treatment did not reduce airway reactivity, showing that these pathologic and physiologic measures of exacerbated disease are independent. We speculate that the reciprocal effect of the allergic response on viral immunity may benefit the host by limiting exacerbation of physiologic responses that are IFN-gamma-dependent.

Keeping Tabs: Are Redundant Marking Systems Needed for Rodents?

We use survival analysis to compare failure of passive integrated transponder (PIT) tags and loss of metal ear tags in 2,277 southern flying squirrels (Glaucomys volans), 124 house mice (Mus musculus), 112 hispid cotton rats (Sigmodon hispidus), and 374 deer (Peromyscus maniculatus) and cotton mice (P. gossypinus). With the exception of cotton rats, failure rates between ear and PIT tags differed by species. Flying squirrels exhibited the highest proportional loss of both tag types and lost ear tags more readily than PIT tags failed. The opposite was true for cotton rats and deer and cotton mice. Most PIT tags appeared to fail shortly after implantation (≤3 days), except for flying squirrels and, to a lesser extent, cotton rats. Ear tags exhibited a consistent rate of loss in flying squirrels. Body mass did not influence failure of PIT tags; however, flying squirrel body mass was associated with increased loss of ear tags. For flying squirrels PIT tag failure increased with the number of times an individual had already received a PIT tag that failed. We provide recommendations for using PIT and ear tags in marking rodents based on species-specific patterns and suggest the combined use of external and internal markers to obtain the most reliable estimates of population parameters.

322. Syngeneic Cotton Rat Cancer Model for Replicating Adenoviral Vectors

Background: Oncolytic adenoviruses are under study as a potential anticancer treatment. Their preclinical antitumor activity; however, has not been effectively translated to the clinic. A contributing factor may be the clinical relevance of immunodeficient mouse tumor xenograft models used to study these vectors. While these demonstrate viral replication in the xenograft, they are limited by the lack of natural host immune responses to the virus, associated toxicity, dissemination and systemic viral replication. Cotton rats (Sigmodon hispidus) are semi-permissive for the replication of human adenovirus and have been used to study these vectors. Until recently this model lacked a transplantable tumor to assess oncolytic activity. We characterized three syngeneic transplantable cotton rat tumor cells lines that support adenovirus replication and oncolysis in this immunocompetent rodent model. Methods: Three tumor cell lines: CCRT, LCRT and VCRT were derived from a spontaneously arising osteosarcoma, and fibrosarcomas of the breast and jaw in animals from an inbred cotton rat colony. The ability of the cells to be infected with adenovirus was examined using an adenovirus expressing green fluorescent protein (Ad.GFP). Viral burst assays were used to determine titers of infective adenovirus produced by each cell line at 4 and 72 hours following infection with wild type adenovirus type-5 (Ad5). Transmission electron microscopy (TEM) was used to visualize the relative number of virions at each time point. We also evaluated replication and oncolysis of the cell lines in vivo. Results: Using Ad.GFP, the cell lines were readily infected and demonstrated GFP expression comparable to human A549 cells. All cell lines showed significant higher (P<0.05) intracellular titers of adenovirus and in supernatants 72 hours after infection compared to 4 hours after infection with Ad5 indicating viral replication and increased number of functional virions. In addition, all the cell lines exhibited greater expression of adenoviral hexon protein at 72 hours than at 4 hours after infection, indicating late transcriptional unit gene activation. The cotton rat cell lines formed tumors in cotton rats when injected subcutaneously. On days 5 and 8, PCR demonstrated 2 to 3-log greater number of Ad5 genome copies in tumors injected with Ad5 compared to those injected with a non- replicating adenovirus (Ad.null). This was consistent for CCRT, LCRT and VCRT. Ad5 slowed tumor growth in cotton rats subcutaneously injected with CCRT and VCRT cells. Despite in vitro oncolysis, no anti-tumor effect was seen in the LCRT tumors with the virus rapidly cleared from the tumor. Conclusions: CCRT, LCRT and VCRT, three novel transplantable cotton rat tumor-derived cell lines demonstrate replication of Ad5 both in vitro and in vivo. In addition, CCRT and VCRT demonstrated in vivo oncolysis. The varied antitumor effect in this model mirrors the results of human clinical trials highlighting the potential relevance of these cotton rat tumor models for assessing replication competent adenovirus vectors.

Concentration ratios for small mammals collected from the exposed sediments of a 137Cs contaminated reservoir

137Cs concentration ratios were computed for small mammals collected from the dried sediments of a partially drained, contaminated reservoir. Soil 137Cs activity concentrations were heterogeneous on small and large spatial scales and had a geometric mean of 253 (range 23–2110) Bq/kg dry weight. Mean 137Cs activity concentrations in composite cotton rat Sigmodon hispidus and cotton mouse Peromyscus gossypinus samples averaged 2480 (range 556–6670) and 471 (range 96–1000) Bq/kg whole body dry weight, respectively. About 50% of the variance in cotton rat tissue 137Cs activity was explained by variation in soil 137Cs activity. Soil-to-animal dry weight concentration ratios averaged 6.0 for cotton rats and 1.2 for cotton mice and were generally similar to 137Cs concentration ratios for herbivorous, homeothermic animals from other contaminated ecosystems. In the RESRAD-BIOTA dose model, the default wet-weight concentration ratio for 137Cs in terrestrial animals is 110 resulting in an estimate of internal and external radiation doses to terrestrial biota that is 44 times more than the dose calculated with the actual measured wet-weight concentration ratio for cotton rats (1.6). These results show that site-specific concentration ratios can significantly affect the estimation of dose.

USE OF COASTAL WETLANDS BY HISPID COTTON RATS (SIGMODON HISPIDUS)

Hispid cotton rats (Sigmodon hispidus) occur primarily in grass-dominated habitats. These habitats abut tidal wetlands along the Gulf and Atlantic coasts of the United States occupied by the marsh rice rat (Oryzomys palustris). Few data document whether cotton rats also occupy wetlands and whether interspecific interactions exist with rice rats. We used livetraps to sample 4 grids that each encompassed wetland and upland habitats near Galveston, Texas. Cotton rats occurred in both upland and wetland habitats. Density of cotton rats was lower in wetlands; their residence time was less in wetlands, which perhaps indicated poorer survival or movement to uplands. Sex ratio, proportion reproductive, and age structure, however, did not differ between upland and wetland habitats. Density of cotton rats and rice rats was negatively correlated. Such density compensation coupled with differences in diel activity and diet minimizes potential for interspecific competition.

Patterns of Avian Nest Predators and a Brood Parasite Among Restored Riparian Habitats in Agricultural Watersheds

In fragmented edge-dominated landscapes, nest predation and brood parasitism may reduce avian reproductive success and, ultimately, populations of some passerine species. In the fragmented agroecosystem of northwest Mississippi, placement of drop-pipe structures has been used as a restoration technique for abating gully erosion along stream banks. These actions have formed small herbaceous and woody habitat extensions into former agricultural lands. We quantified species relative abundances, species richness, and evenness of avian nest predators and a brood parasite within four categories of constructed habitat resulting from drop-pipe installation. Differences in the abundance of two nest predators, cotton mouse (Peromyscus gossypinus) and blue jay (Cyanocitta cristata), were observed among constructed habitats. However, relative abundances of other predators such as common grackle (Quiscalus quiscula), American crow (Corvus brachyrhynchos), and hispid cotton rat (Sigmodon hispidus), and the obligate brood parasite brown-headed cowbird (Molothrus ater) did not differ among four habitat categories. Although species richness, abundance, and evenness of potential nest predators were generally similar among the constructed habitats, predator species composition varied, suggesting that these habitats supported different predator communities. This difference is important because as each predator species is added to or deleted from the community, variation may occur in the framework of prey search methods, predator strategies, and potentially overall predation pressure. We suggest that land managers using drop-pipes as part of stream restoration projects allow for the development of the constructed habitat with the largest area and greatest vegetative structure.

Hypergastrinaemia induced by partial corpectomy results in development of enterochromaffin‐like cell carcinoma in male Japanese cotton rats

Background: Among inbred female cotton rats (Sigmodon hispidus) 25%–50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin‐like (ECL)‐cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Methods: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%–90% of the corpus. A control group was sham‐operated. Results: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier‐Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier‐Munger. Conclusions: ECL‐cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL‐cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.

NITROGEN CONCENTRATION OF STOMACH CONTENTS AS AN INDEX OF DIETARY NITROGEN FOR SIGMODON HISPIDUS

We examined the reliability of using nitrogen concentration of stomach contents from hispid cotton rats (Sigmodon hispidus) as an index of dietary nitrogen. Stomach contents of hispid cotton rats fed pelleted diets varying in nitrogen concentration were analyzed for stomach nitrogen. Regression analysis revealed a positive linear relationship between stomach and dietary nitrogen, but the relationship was not 1:1. Thus, inverse estimation of the regression equation can be used to adjust for a lack of a 1:1 ratio to obtain more reliable and accurate estimates of diet quality. Although we expected this relationship to be robust in its application to field studies, the pelleted diet model consistently underestimated dietary nitrogen during model evaluation experiments with natural forages. We conclude that the applicability of using nitrogen concentration of the stomach contents of cotton rats as an index to dietary nitrogen is dependent on the level of accuracy and precision required in estimating nitrogen concentration of foods consumed.

Cotton rat Sihi-M3 is a minimally oligomorphic Mhc I-b molecule that binds the chemotactic peptide fMLF under stringent conditions. Evidence that positive selection drives inter-species diversity of residues interacting with the termini of short peptides.

The leading model for class I-b evolution suggests non-polymorphic I-b genes evolve by gene duplication from polymorphic I-a genes. We recently found N-formyl peptide-specific orthologs of the class I-b gene H2-M3 in the rodent subfamily Sigmodontinae. To test if sigmodont M3 is a I-b gene, we sequenced M3 from wild cotton rats ( Sigmodon hispidus) diverse at the class II locus, Sihi-DQA. These haplotypes carry a single allele of M3 that closely resembles H2-M3. However, peptide-binding assays showed that cotton rat M3 bound the chemotactic N-formylpeptide fMLF better than did rat or mouse M3. The Ala116-->Lys substitution in cotton rat M3 might enhance binding of fMLF and is one of eight residues of M3 that interact with ligand residues P3 and P4 and that are positively selected, with a d(N) /d(S) ratio of 1.8. Thus, M3 is a class I-b gene in both sigmodontine and murine murids, but positive selection operates on a small subset of residues in the traditionally defined antigen recognition site.

Lymphoproliferative responses of splenocytes from wild cotton rats (Sigmodon hispidus) following acute exposure to Aroclor 1254.

Lymphoproliferative responses of splenocytes from wild cotton rats (Sigmodon hispidus) following acute exposure to Aroclor 1254.

Ecotoxicological Risks Associated with Land Treatment of Petrochemical Wastes. II. Effects on Hepatic Phase I and Phase II Detoxification Enzymes in Cotton Rats

The purpose of this study was to evaluate possible exposure and resultant hepatic effects of petrochemical waste on cotton rats (Sigmodon hispidus) living on landfarmed sites. Male and female cotton rats were collected in summer, fall, and winter from four landfarm sites and four ecologically similar reference sites. Hepatic methoxyresorufin O-deethylase (MROD) activity was significantly induced in male and female rats collected from landfarms compared to rats collected from reference sites. In contrast, changes in ethoxyresorufin O-deethylase (EROD) activity were inconsistent due to season, sex, and treatment variation. A significant decrease in EROD and MROD activity was found in cotton rats held for 48 h prior to sacrifice compared to rats euthanized on the day of capture. These results indicate that when using hepatic EROD and MROD activities as biochemical markers of exposure to aryl hydrocarbon receptor agonists, animals should be euthanized as quickly as possible after capture. The cotton rats collected from one landfarm unit exhibited a pattern of consistent elevation of EROD, MROD, and pentoxyresorufin O-deethylase (PROD) activity. This unit also had a pattern of elevated CYP1A2 protein expression determined by Western blotting. There were no consistent alterations from contaminant exposure on hepatic glutathione S-transferase (GST) activity, glutathione levels, or CYP1A1 protein. Hepatic EROD and MROD activities varied considerably between seasons and sex of rats. In conclusion, consistent induction of hepatic EROD and MROD activities in cotton rats was found in three out of four sampled landfarm sites compared to the rats collected from the reference sites, indicating exposure to contaminants--likely polyaromatic hydrocarbons.