Male Cotton Rats Research Articles

Age-related glomerular lesions with albuminuria in male cotton rats.

The increased prevalence of aging-related chronic kidney disease (CKD) among humans is a problem worldwide. Aged cotton rats (Sigmodon hispidus) are considered novel model animals for studying CKD, especially as the females develop severe tubulointerstitial lesions with anemia. To investigate the renal pathologic features in aged male cotton rats and their characteristic glomerular injuries, the animals were divided into young, adult, old-aged, and advanced-aged groups (1-4, 5-8, 9-12, and 13-17 months, respectively) and pathologically analyzed. Anemia and renal dysfunction, as indicated by hematologic and serologic parameters, were significantly milder in the advanced-aged males than in the old-aged females. The males had increased urinary albumin-to-creatinine ratios from the old-age period, with the advanced-aged males having significantly higher levels than those in the old-aged females and young males. The old-aged females did not show clear glomerular injuries, whereas the advanced-aged males showed membranous lesions characterized by irregular and thickened glomerular basement membranes (GBMs). Characteristically, several large-sized projections from the GBM toward the podocytes were observed by microscopy, and podocytes covering these projections effaced their foot processes. The advanced-aged males showed aging-related IgG immune-complex depositions in the paramesangial regions and along the GBM. Furthermore, the positive reaction for podocin (a podocyte molecule) was granulated along the GBM. Thus, we clarified the albuminuria associated with altered glomerular structures in advanced-aged cotton rats, and that these phenotypes were closely associated with aging. These data help to clarify the aging-related pathogenesis of glomerular injury.

Mesocarnivores affect hispid cotton rat (Sigmodon hispidus) body mass

Predator communities are changing worldwide: large carnivores are declining while mesocarnivores (medium-sized mammalian predators) are increasing in number and ecological influence. Predator choice of prey is not random and different predators select prey with different characteristics. Changes in predator communities can change predation patterns experienced by prey. Little is known about how mesocarnivore communities influence prey morphology. We used 14 years of mark-recapture data to investigate how mesocarnivore exclusion affected body mass of hispid cotton rats (Sigmodon hispidus). Finding adult male cotton rats were 9% heavier with mesocarnivore exclusion, we developed hypotheses to explain this observation. Greater adult male body mass in exclosures resulted from: (1) a non-significant trend of increased survival of large males, (2) faster juvenile male growth during the fall and a similar non-significant trend among adult males, and (3) spatial partitioning by size among males. Taxa-specific predation rates (i.e., rates of predation by snakes, raptors, or mesocarnivores) did not differ among male body mass classes. Mesocarnivores disproportionately preyed on large females while raptors targeted small females, but female body mass was not influenced by mesocarnivore exclusion. Changes in predator communities can result in multiple small effects that collectively result in large differences in prey morphology.

Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity.

Obesity induces metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases and has become a global health concern. Recent studies imply that fat accumulation in nonadipose tissue correlates with metabolic disorders. However, there are no suitable animal models to evaluate this phenomenon. This study investigated the characteristics of metabolic disorders found in cotton rat (Sigmodon hispidus). Blood biochemical examinations revealed that cotton rats, predominantly males, developed hyperinsulinemia, hyperglycemia, and dyslipidemia when fed a normal diet. The islets increased in size through β-cell hyperplasia, which was associated with serum insulin level in both sexes, strongly indicating insulin resistance. In male cotton rats, oxidative stress was observed in β cells, and macrophage infiltration into the visceral white adipose tissue was reported, both of which were associated with serum insulin level without visceral obesity. In contrast, female cotton rats developed hyperinsulinemia without histopathological changes that were reported in males. Adipocytes were found to be accumulated in the pancreas but not in the liver of both sexes during aging. Pancreatic fat accumulation was associated with the serum insulin level only in females. Taken together, cotton rats developed metabolic disorders associated with visceral fat inflammation in the absence of obesity. In addition, pancreatic ectopic fat may also be related to the early stages of these conditions. Thus, the cotton rat may serve as a novel and useful model for metabolic disorders characterized by visceral adipose inflammation and ectopic fat accumulation in the pancreas without obesity.

Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes.

The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9months of age. The severity of these lesions progressed from 10months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.

Effects of an invasive ant and native predators on cotton rat recruitment and survival

We used the imported red-fire ant (Solenopsis invicta; hereafter fire ant) and hispid cotton rat (Sigmodon hispidus) as model species to address the population-level effects of an invasive ant on a semiprecocial small mammal. We stocked cotton rats into 8 enclosures, implementing a 2-way factorial design with predator (ambient or excluded) and fire ant (ambient or reduced) treatments as factors. We trapped monthly from June 2012 to June 2013 and calculated monthly recruitment and survival. Rats in enclosures with ambient predators had a risk of mortality approximately 2 times greater than rats in enclosures with predators excluded. The risk of mortality was 3 and 4.5 times greater for female and male cotton rats, respectively, in enclosures with ambient fire ants and predators compared to enclosures with reduced fire ants and excluded predators. We found no effects on recruitment. Our results indicate that native predators had the greatest influence on cotton rat populations. Nevertheless, in the absence ...

Prospective Studies ofBartonellaof Rodents. Part I. Demographic and Temporal Patterns in Population Dynamics

The temporal dynamics of Bartonella infections in a rodent community were described by repeatedly capturing and sampling individual animals. Among six rodent species, from which bartonellae were isolated, cotton rats (Sigmodon hispidus) accounted for > 98% of the bacteremic animals. All cotton rats captured four or more times were Bartonella-culture positive at least once. The lowest monthly prevalence of Bartonella in cotton rats was in June (49%) and the highest was in October (95%). Prevalence of Bartonella infection increased to > 90% among juvenile and subadult rats before declining to < 40% among the largest-oldest individuals. Bacteremia levels ranged between 40 and 4.0 x 10(6) colony forming units (CFU) per 1 mL of blood. Male cotton rats had significantly higher CFUs than females (p = 0.006). The median of Bartonella bacteremia decreased monotonically by age group among cotton rats. Although Bartonella infections were highly prevalent among cotton rats, only 8.5% of rats had reactive antibodies at titers of > or = 1:32 and none had antibodies titers of > 1:256.

ECL-cell derived gastric cancer in male cotton rats dosed with the H2-blocker loxtidine.

Spontaneously hypergastrinemic cotton rats (Sigmodon hispidus) develop tumors that have the phenotype of an adenocarcinoma but most likely originate from the enterochromaffin-like (ECL) cells. Among inbred animals approximately 50% of the females, but <1% of males develop spontaneous gastric carcinomas. Gastrin is the principle carcinogen in this model, as >4 months of hypergastrinemia results in carcinoma, but a gastrin receptor antagonist prevents carcinomas. Carcinomas can also be induced by partial corpectomy. In the present study, the insurmountable H2-receptor antagonist loxtidine (200 mg/kg/day) was given to male cotton rats for 6 months. The loxtidine-dosed animals developed hypergastrinemia, whereas control animals remained normogastrinemic. At termination, 4 of 5 cotton rats had cancer located to the oxyntic mucosa, whereas 1 animal had dysplasia. The gastric mucosa of all of the control animals was normal. In the dysplastic mucosa of loxtidine-dosed animals there was a marked increase in chromogranin A-positive cells, where numerous groups of cells also stained positive with the Sevier-Munger technique. In areas of high proliferation and cancer there were also histidine decarboxylase, chromogranin A, and Sevier-Munger-positive cells, altogether indicating an ECL cell origin of the tumors. This represents an interesting animal model where ECL cell-derived gastric cancer can be induced by pharmacological acid inhibition in 6 months.

Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.

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.

Immune function and hematology of male cotton rats ( Sigmodon hispidus) in response to food supplementation and methionine

We examined effects of supplementation of food quantity and quality (=enhanced methionine) on hematologic and immunologic parameters of wild, but enclosed, adult male cotton rats ( Sigmodon hispidus) in north-central Oklahoma. Sheet metal enclosures were stocked with a high density of wild-caught cotton rats (160 animals/ha) and randomly assigned a treatment of no supplementation, mixed-ration supplementation or methionine-enhanced supplementation. Aside from small increases in counts of red blood cells and hematocrit levels, most indices of erythrocytic characteristics were not affected by supplementation with the mixed-ration or enhanced methionine. In contrast, platelet counts were highest in mixed-ration and methionine treatments and counts of total white blood cells were highest with methionine supplementation, albeit relative proportions of different leukocytes did not differ among treatments. Immunologically, neither delayed-type hypersensitivity response nor hemolytic-complement activity differed among treatments. Supplementation of food quantity and quality did not broadly affect hematologic parameters and immune function of male cotton rats, but enhanced platelet and leukocyte counts may confer advantages to overall health. Clarification of the role of such effects on population limitation or regulation requires additional research.

Hypergastrinemia induced by partial corpectomy results in ECL-cell carcinoma in male cotton rats

Approximately 50 percent of females and one percent of males in a strain of Japanese cotton rats (Stgmodon hispidns) develop spontaneous enterochromaffm-like(ECL)-ceU derived gastric carcinomas and have hypergastrinemia secondary to gastric hypo/anacithty. The mechanism behind the hypo/anacidity is unknown. We have found carcinomas in all female cotton rats with spontaneous hypergastrinemia lasting more than four months. These animals represent an excellent model for studying ECL-cell carcinogenesis. The development of these tumors is prevented by a gastrin antagonist as well as by a somatostatin analogue. We have therefore previously argued that the carcinogenesis is due to hypergastrinemia. Whether induced hypergastrinemia would result in ECL-cell carcinomas cotton rats has not been examined. We therefore performed partial corpectomy, an operation that has resulted in persistent hypergastrinemia and ECDcell derived tumors in Sprague-Dowley rats more than two years postoperatively. Male cotton rats were chosen as they have the lowest incidence of spontaneous carcinomas. Male cotton rats were operated b)' ~n ia l corpectomy aiming at removal of 90% of the corpus. A control group was sham-operated. All animals were given B 12-injections monthly. Serum gastrin was measured every second month. At termination the stomach was examined histologically (haematoxylin and eosin) and immunohistochemically with an antibody against chromogranin A, a neuroendocrine cell marker. All partially corpectomized animals developed persistent hypergastrinemia and ECL-cell derived cancer after six months. Immunohistochemieal examination confirmed a neuroendocrine origin of the tumors. This study demonstrates that ECL-ceU carcinomas can be induced in male cotton rats in six months. The results support our previous statement that spontaneous tumors developing in cotton rats are caused by gastric hypoacidity and hypergastrinemia. Given persistent hypergastrinemia, ECL--cell carcinomas will develop in cotton rats independent of sex within a relatively short period of time.

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.

Toxicity of 2,4,6-TrinitrotoIuene (TNT) in Hispid Cotton Rats (Sigmodon hispidus): Hematological, Biochemical, and Pathological Effects

The contamination of soil and water with munitions chemicals and their degradation products has been reported at certain munitions production waste disposal sites and at certain Army installations. The effects of 2,4,6-trinitrotoluene (TNT) on wild cotton rats ( Sigmodon hispidus) were evaluated to identify target organ toxicity that could be used to develop biomarkers for exposure assessment for ecological and health risks. The oral LD50 values for TNT in corn oil were 607 and 767 mg/kg body weights for male and female cotton rats respectively. Hematological, pathological, and biochemical effects of TNT were determined after daily oral gavage of TNT in corn oil at doses of 0, 75.9, 151.8, and 303.5 (males) or 0, 96, 192, and 384 mg/kg (females) for 7 days. Cotton rats treated with TNT showed an increase in spleen weights in males (303.5 mg/kg) and in females (192 and 384 mg/kg). Cotton rats of both sexes treated for 7 days with TNT had marked hemolytic anemia with reduced erythrocytes, hemoglobin, and hematocrit in high-dose groups; methemoglobin levels were elevated significantly in males at mid and high dose. Hepatic drug metabolizing enzyme analysis revealed that microsomal O-dealkylation of methoxy, ethoxy, and pentoxy resorufin were elevated in male (high dose) cotton rats. The activity of hepatic glutathione S-transferases (GST) was significantly elevated in male (mid and high dose) and female (all doses) cotton rats exposed to TNT. Histopathological analysis of spleen revealed mild to marked splenic congestion with mild extramedullary hematopoiesis, hemosiderosis, and lymphoid hyperplasia in male and female cotton rats treated with TNT (all doses). Liver weights were increased in males (mid and high dose) and in females (high-dose group). In the high-dose groups, histological changes in liver (mild to moderate hepatocellular hypertrophy, increased hemosiderin pigment in Kupffer cells) in both sexes, and in testis (premature exfoliation of spermatozoa from dilated seminiferous tubules) were observed (mid and high dose). These results suggest that hepatic GST and hemolytic anemia may be biomarkers in cotton rats of terrestrial contamination with TNT or other nitroaromatic explosive compounds.

Transmission of Black Creek Canal virus between cotton rats.

Black Creek Canal (BCC) virus is a hantavirus associated with hantavirus pulmonary syndrome in southeastern North America. The virus was isolated from the spleen of a cotton rat (Sigmodon hispidus) trapped in southern Florida. Our previous studies have shown that we could consistently infect male cotton rats with BCC virus in the laboratory. These animals became persistently infected and virus could be detected in salivary glands, urine, and feces. In this report we show: (1) female and male cotton rats are equally susceptible to BCC virus infection, (2) susceptibility to infection was not influenced by age, (3) all inoculated rats transmitted the infection to uninoculated cage mates, and (4) offspring of infected rats became infected despite the presence of high maternal antibodies. The course of BCC virus infection, as determined by antibody response and the ability to isolate or detect virus, appeared to be similar regardless of whether the rats obtained their infection by inoculation or contact with inoculated rats. J. Med. Virol. 60:70-76, 2000. Published 2000 Wiley-Liss, Inc.

Dose-response relationships for cytochrome P450 induction by phenobarbital in the cotton rat ( Sigmodon hispidus)

The induction of a hepatic pleiotropic response, including increase in liver/body weight ratio, induction of hepatic CYP2B and CYP3A protein and catalytic activity, and hepatic microsomal epoxide hydration activity, was investigated in male cotton rats ( Sigmodon hispidus) administered graded dietary concentrations (0–1500 ppm) of phenobarbital (PB) for 14 days. A dose-dependent induction of each endpoint was observed, although plateaus in the various dose-response curves were not obtained, and ED 50 values (PB concentrations associated with half-maximal responses) for the various endpoints were not able to be calculated. A maximal 1.31-fold increase, compared to the control value, in liver/body weight ratio was observed, while microsomal epoxide hydration activity was increased as much as 3.6-fold by PB administration. Pentoxy- and benzyloxyresorufin O-dealkylation and testosterone 16 β-hydroxylation activities (considered to be relatively selective for CYP2B in the Norway rat ( Rattus norvegicus)), were induced maximally less than five-fold. Testosterone 6 β-hydroxylation (considered to be relatively selective for CYP3A in R. norvegicus) was induced maximally less than two-fold. Maximal induction of 7-ethoxy-4-trifluoromethyl-coumarin O-deethylation was 18-fold, compared to the control rate. Western blotting studies indicated that hepatic microsomal proteins immunoreactive with polyclonal antisera to R. norvegicus CYP2B1 or CYP3A1 were induced, in a dose-responsive manner, by PB in the cotton rats. These results indicate that the cotton rat responds to PB treatment with a coordinate pleiotropic response similar to that displayed by R. norvegicus, although the substrate specificity of the induced proteins appears to differ between the two rodent species.

Pathogenesis of a North American hantavirus, Black Creek Canal virus, in experimentally infected Sigmodon hispidus.

This report describes the first detailed analysis of the replication, persistence, and excretion of a North American hantavirus in its natural rodent reservoir. Black Creek Canal virus was isolated from Sigmodon hispidus (cotton rat) shortly after the identification of a hantavirus pulmonary syndrome (HPS) case occurring in southern Florida. Six-week-old male cotton rats were inoculated subcutaneously with 1,000 tissue culture infectious doses. Viral complementary RNA (vcRNA) was quantified as a means of determining the site(s) of viral activity (transcription and replication). In the first few weeks post inoculation (pi), vcRNA was detectable in every tissue examined except blood. The quantities of vcRNA decreased over time, and by five months pi it could be detected only in the brain. In addition to using a quantitative polymerase chain reaction (QPCR) as a means of measuring viral replication/transcription, attempts were made to reisolate virus from all tissue samples taken. Virus could be isolated from every solid tissue examined, and the titers appeared to decrease over time, similar to the QPCR results. However, in contrast to the QPCR results, infectious virus was still routinely detectable at low levels in adrenal gland, liver, kidney, and testicle 150 days pi. Although results of testing for vcRNA in the blood were uniformly negative, infectious virus was detected at one week pi, reached highest titers at two weeks, and decreased dramatically by three weeks. After three weeks pi, infectious virus could only be detected sporadically in blood. Virus was isolated from urine collected during the first 70 days pi and throughout the entire study period in feces and wet bedding. These data indicate that the viral infection can be separated into an acute phase associated with high virus titers, and a chronic or persistent phase associated with lower virus titers and continued shedding of virus in excreta.

Sensitivity of wild cotton rats (Sigmodon hispidus) to the immunotoxic effects of low-level arsenic exposure.

Arsenic is a ubiquitous contaminant of many toxic waste sites around the country and experimental animal trials have indicated that arsenic may be immunotoxic to laboratory rodents. Because wild rodents such as the herbivorous cotton rat (Sigmodon hispidus) reside on many of these toxic waste sites, we explored the sensitivity of their immune systems to oral exposures of environmentally relevant concentrations of inorganic arsenic. We exposed adult male cotton rats (n = 36) to either 0 (controls), 5 (low dose), or 10 (high dose) ppm sodium arsenite in drinking water for 6 weeks. Daily food intake decreased in a dose-dependent manner, ranging from an average of 10.03 +/- 0.45 in the high-dose group to 11.27 +/- 0.42 (SE) g/animal/day in the control group. Mass of testes in the low-dose group increased significantly compared to controls, but there was no difference between the high-dose and control groups. Masses of liver, kidney, adrenals, popliteal lymph nodes, spleen, epididymides, and seminal vesicles and selected hematological parameters were unaffected by arsenic exposure. In vivo cell-mediated immunity, as measured by a phytohemagglutinin-hypersensitivity response to an intradermal challenge, was suppressed 30% in the low-dose group compared to controls; however, responses of those receiving a high dose of arsenic were similar to controls. Arsenic treatment did not have a measurable impact on lymphoproliferative responses of cultured splenocytes to the mitogens Concanavalin A and Pokeweed mitogen, or to the lymphokine interleukin-2. We also observed no impact of low-level arsenic exposure on macrophage phagocytic activity and tumoricidal activity of lymphokine-activated killer cells in vitro. It is possible that malnutrition caused by decreased food intake may eventually lead to atrophy of lymphoid organs and render animals more susceptible to environmental pathogens. However, direct effects of low-level arsenic exposure on immune function of cotton rats was minimal (a moderate depression in the in vivo cell-mediated immunity assay) and may not be clinically relevant with regard to susceptibility to disease in the wild.

Tumoricidal Activity of Lymphokine-Activated Killer Cells During Acute Protein Restriction in the Cotton Rat ( Sigmodon hispidus)

Habitat-induced alterations of immune system function have been implicated in the regulation of survival rates in wild herbivore populations. Protein availability in the diet has been shown to fluctuate with density and influence immunity in hispid cotton rats ( Sigmodon hispidus), a common herbivorous rodent of the southeastern United States. In this study, we examined the impact of short-term, moderate restrictions in dietary protein on the tumoricidal activity of lymphokine-activated killer (LAK) cells in the spleen of subadult male cotton rats in captivity. Animals were fed complete, isocaloric diets containing either 20% casein (high quality diet), or one of three moderate levels of protein (10, 8, or 5% casein) for two weeks prior to assessing LAK cell activity in vitro in the presence of YAC-1 tumor cells. Moderate restrictions in protein resulted in depressed body growth, although all animals gained mass during the second week of the trial, without significant increases in food intake. Immune organ development and cellularity were suppressed in moderately restricted cotton rats when compared to those on a high quality diet. Tumoricidal activity of LAK cells against YAC-1 targets were significantly altered by diet treatments, being elevated in the group fed a diet containing 10% casein. There was a general tendency for increased LAK cell activity among those fed one of the three moderate quality diets, but observed suppressions in splenic cellularity tended to result in a slight decline in total lytic capacity of spleens.

Habitat Fragmentation and Movements of Three Small Mammals (Sigmodon, Microtus, and Peromyscus)

We studied the effects of habitat fragmentation on the movements of cotton rats (Sigmodon hispidus), deer mice (Peromyscus maniculatus), and prairie voles (Microtus ochrogaster) living in a fragmented landscape using 7.7 yr (1984—1992) of mark—recapture data. The study area included three kinds of 0.5—ha blocks: single large patches (5000 m2), clusters of medium patches (27 88 m2), and clusters of small patches (32 m2). We tested three predictions regarding animal movements. First, animals should move longer distances as fragmentation increases. Second, the proportion of animals moving will decrease as fragmentation increases. Third, species will show more movement from putative sources to putative sinks. In support of our first two predictions, all species (except male cotton rats) moved farther, and lower proportions of animals moved, as fragmentation increased. In testing our third prediction, we found no trends, for all species, between patch size and the net number of animals a block either imported or exported, indicating source—sink dynamics were probably not occurring on our study site. Furthermore, animals of all species (except female deer mice) switched more frequently to blocks of larger patches. For prairie voles in the spring and deer mice in the summer, relative abundances among blocks predicted from a Markov matrix model of switching probabilities showed high congruence with the actual abundances, indicating movement and abundances were related. In both cotton rats and prairie voles but not in deer mice, more juveniles and nonreproductive animals switched between blocks than did adults or reproductive animals. Deer mice switched more frequently than did either cotton rats or prairie voles; the latter species switched in similar frequencies. We discuss the implications of our data for modeling and conservation.

Fluorosis in a wild cotton rat (Sigmodon hispidus) population inhabiting a petrochemical waste site.

We have developed an in situ mammalian model for evaluating environmental contamination using wild cotton rats. In a series of experiments, 200 male cotton rats were captured during 4 collection periods (spring 1991 = 35; fall 1991 = 60; spring 1992 = 53; fall 1992 = 52). A total of 103 of these cotton rats were captured from control sites, and the remaining 97 were captured from an abandoned oil refinery. All sites were located in the vicinity of Cyril, Oklahoma. There were alterations in the incisors of cotton rats captured from the refinery site. Normal color of cotton rat incisors is deep yellow-orange, which is imparted by a pigment normally produced by ameloblasts. Grossly, the upper incisors of 37 of 97 rats and lower incisors of 54 of 97 rats were affected. The affected incisors were white, chalky, and thin with striations and erosions of the enamel. Microscopic examination revealed that there were dysplastic and necrotic changes in the ameloblasts. The bone fluoride levels were significantly higher in rats captured from the refinery as compared to the rats captured from the control sites.