How common are common fragile sites in humans: interindividual variation in the distribution of aphidicolin-induced fragile sites

To obtain an estimate of the variation in common fragile sites (CFSs) among individuals, aphidicolin (APC)-induced chromosomal breakage data were analyzed for 20 karyotypically normal adult humans. As it is specifically designed to meet the analytical requirements for considering fragile sites as presence/absence characters in single individuals, the FSM methodology (B?hm et al., 1995) was used to statistically distinguish fragile from nonfragile sites. These analyses indicated that the APC-induced fragile sites are not ubiquitous but vary extensively among individuals; the per-individual number of fragile sites ranged from as few as seven to as many as 20. Of the 45 different sites identified as fragile, 19 (42%) occurred in more than half of the individuals, but only two sites (3p14 and 16q23) were fragile in all of the individuals; 12 (27% of the total) were fragile in single individuals only. Although these analyses provide statistical confirmation (and initial estimates of population variation) for 43 of the 88 APC-inducible fragile sites currently recognized as occurring among humans, they are consistent with the hypothesis that many of the currently recognized human CFSs have been erroneously identified. These results indicate the need for per-individual statistical identification of CFSs for larger samples of individuals and that studies of particular fragile sites should be conducted on individuals documented to be fragile at the loci under consideration.     

Genic variation in the deer mouse,Peromyscus maniculatus,in a small geographic area

Genic variation was examined with starch and polyacrylamide gel electrophoresis at 14 loci in 12 populations of Peromyscus maniculatus nubiterrae from a small part of the Appalachians in eastern Tennessee and western North Carolina. Polymorphism was observed at eight loci with no significant correlations between frequency of common genotypes or alleles and altitude. Average individual heterozygosity (\-H) values were low for P. maniculatus whether using only slow evolving loci (mean = 3.0%) or both slow and fast evolving loci (mean = 4.9%). No significant correlation was present between altitude and \-H. Interlocality variation of \-H was as great in this study as previously reported for P. maniculatus over larger geographic areas. Rogers' coefficients of genetic similarity of paired combinations of populations based on slow evolving loci (range of 0.941 to 0.997) or based on slow and fast evolving loci (range of 0.858 to 0.974) showed all populations to be highly similar. Ranges of similarity values observed in the present study were as great as those previously reported for P. maniculatus over a larger geographic area.     

Hemoglobin polymorphism in the deer mouse,Peromyscus maniculatus

Horizontal starch gel electrophoresis reveals three hemoglobin phenotypes in natural populations of the deer mouse, Peromyscus maniculatus,from northern Arizona. Phenotypic variation is controlled by a single locus. A sample of deer mice from Michigan was monomorphic for a multiple-banded phenotype. Hemoglobin polymorphism was also observed in Arizona samples of the species Peromyscus boylii.This investigation was supported by Public Health Service Research Grant R01-GM12190.     

Persistent Sin Nombre virus infection in the deer mouse (Peromyscus maniculatus) model: sites of replication and strand-specific expression

To address Sin Nombre (SN) virus persistence in deer mice, we sacrificed experimentally infected deer mice at eight time points from day 21 to day 217 postinoculation (p.i.) and examined their tissues for viral nucleocapsid (N) antigen expression and both negative-strand (genomic) and positive-strand (replicative/mRNA) viral S segment RNA titers. All the animals that we inoculated developed persistent infections, and SN virus could be isolated from tissues throughout the course of infection. The transition from an acute to a persistent pattern of infection appeared to occur between days 60 and 90 p.i. Beginning on day 60 p.i., the heart, brown adipose tissue (BAT), and lung retained antigen expression and genomic viral RNA the most frequently. We found a statistically significant association among the presence of replicative RNA in the heart, lung, and BAT, widespread antigen expression (in > or =5 tissues), and RNA viremia. Of these three tissues, the heart retained negative-strand RNA and viral N antigen the most consistently (in 25 of 26 animals). During persistence, there were two distinct patterns of infection: restricted versus disseminated tissue involvement. Mice with the restricted pattern exhibited N antigen expression in < or =3 tissues, an absence of viral RNA in the blood, neutralizing antibody titers of < or =1:1,280 (P = 0.01), and no replicative RNA in the heart, lung, or BAT. Those with the "disseminated" pattern showed N antigen expression in > or =5 tissues, neutralizing antibody titers of 1:160 to 1:20,480, replicative RNA in the heart, lung, and BAT at a high frequency, and RNA viremia. Virus could be isolated consistently only from mice that demonstrated the disseminated pattern. The heart, lung, and BAT are important sites for the replication and maintenance of SN virus during persistent infection.     

Morphological analysis of hair in the hr-2 mutant deer mouse (Peromyscus maniculatus)

Skin from 36 hairless deer mice (Peromyscus maniculatus) homozygous for the recessive hr-2 mutation were analyzed for structural defects in hair and hair loss. Comparison of mutant to wild-type hairs demonstrated characteristic abnormalities in cellular organization, hair shape, length, and fragility. Matings between mutants homozygous for the hr-2 gene and for a second mutation producing hairlessness in deer mice, hr-1, showed that these two genes were nonallelic. Structural abnormalities in hairs associated with the expression of this gene suggest that its primary effect may be on the epidermis.     

Photoperiodic time measurement in the male deer mouse, Peromyscus maniculatus

Weanling male deer mice, Peromyscus maniculatus, were exposed for three weeks either to light-dark (LD) cycles with periods (T=L+D) ranging from T=23 (1L:22D) to T=25.16 (1L:24.16D) or to 24-h LD cycles with photoperiods ranging from 1 (1L:23D) to 19 (19L:5D) h. Both the circadian locomotor activity rhythms and the response of the reproductive system to these LD cycles were assessed. The results demonstrate that the photoperiodic effectiveness of light depends on the phase of the light relative to the animal's circadian system, as marked by the circadian activity rhythm. Light falling during the animal's subjective night, from activity onset to at least 11.8 h after activity onset, stimulates growth and maturation of the reproductive system, whereas light falling during the rest of the circadian cycle is nonstimulatory.     

The genetic heterogeneity of deer mouse populations (Peromyscus maniculatus) in an insular landscape

A survey of the genetic variability in deer mouse populations was performed using specimens collected from six different islands on a lake covering approximately 50 km². Random amplified polymorphic DNA (RAPD) was used to measure the extent of the genetic differences in this insular system. An analysis of molecular variance (AMOVA) revealed that populations are clearly separated at this microgeographic scale (F _st = 0.13863; P < 0.001). The homogeneity of molecular variance test (HOMOVA) indicated that within-population levels vary greatly (B _p = 0.76831; P < 0.001). The within-population molecular variance was found to be mainly correlated with the accessibility of the islands, computed as the inverse of the geographic distance separating an island from the lakeshore (r = 0.916; P < 0.003). Received: March 5, 1999 / Accepted: July 16, 1999     

Phenotypic plasticity in skull and dental morphology in the prairie deer mouse (Peromyscus maniculatus bairdii)

Morphologists and systematists have long suspected that dietary consistency can affect skull and dental form in mammals. We examined plasticity of skull shape and tooth morphology in prairie deer mice (Peromyscus maniculatus bairdii) by feeding mice diets that differed in consistency but not nutritional quality. Shape differences were analyzed qualitatively and quantitatively, using both landmark-based morphometrics and traditional distance measurements. Mice fed a gruel made of laboratory chow soaked in water differed from those fed hard blocks of chow by a slight anterior shift in the incisor tips a narrowed zygomatic plate, a reduction in size of the masseteric tubercles, an overall decrease in skull size in lateral view, and an increase in overall size in ventral view. Disparities between our results and previous studies may be due to the differences in behavior between the inbred, relatively inactive laboratory strains commonly used in experimental studies and the outbred, constantly active species used here. Also, in contrast to previous studies, the statistical analysis employed here took into account both family relationships of the animals and the large number of statistical comparisons performed. Failure to consider these factors would have resulted in an exaggerated estimate of the effects of diet on skull form and may taint other studies that have explored the same aspects of plasticity. © 1996 Wiley-Liss, Inc.     

Shedding and intracage transmission of Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus) model

The mechanism(s) by which Sin Nombre (SN) hantavirus is maintained in deer mouse populations is unclear. Field studies indicate that transmission occurs primarily if not exclusively via a horizontal mechanism. Using an experimental deer mouse infection model in an outdoor laboratory, we tested whether infected rodents shed SN virus in urine, feces, and saliva, whether infected mice transmit infection to na?ve cage mates, and whether infected dams are able to vertically transmit virus or antibody to offspring. Using pooled samples of urine, feces, and saliva collected from mice infected 8 to 120 days postinoculation (p.i.), we found that a subset of saliva samples, collected between 15 and 90 days p.i., contained viral RNA. Parallel studies conducted on wild-caught, naturally infected deer mice showed a similar pattern of intermittent positivity, also only in saliva samples. Attempts to isolate virus through inoculation of cells or na?ve deer mice with the secreta or excreta of infected mice were uniformly negative. Of 54 attempts to transmit infection by cohousing infected deer mice with seronegative cage mates, we observed only a single case of transmission, which occurred between 29 and 42 days p.i. Dams passively transferred antibodies to neonatal pups via milk, and those antibodies persisted for at least 2 months after weaning, but none transmitted infection to their pups. Compared to other hantavirus models, SN virus is shed less efficiently and transmits inefficiently among cage mates. Transmission of SN virus among reservoir rodents may require factors that are not required for other hantaviruses.     

Bioenergetic benefits of huddling by deer mice (Peromyscus maniculatus)

Both short photoperiod and communal social living conserve metabolic energy by deer mice held in thermal neutral ambient temperatures. Initial socialization was energetically more costly than solitary living, but huddling behaviors reduced thermal conductance and mass specific metabolic rate by 30% within 5 days. While short photoperiod reduced metabolic energy expenditure by decreasing thermoregulatory demand, huddling mediated behavioral conservation was achieved with hyperthermic core temperatures.     

Developmental plasticity in aerobic performance in deer mice (Peromyscus maniculatus)

While several studies have examined the abiotic effects of altitude (low ambient temperatures and hypoxia) on the aerobic performance of small mammals, few have explored the effects of development and maturation at different altitudes on aerobic performance as adults. We examined the basal metabolism and aerobic performance of deer mice (Peromyscus maniculatus) under four different developmental and testing regimes: (1) reared (gestation through weaning) and tested at high altitude; (2) reared and tested at low altitude; (3) reared at low altitude and tested at high altitude after acclimation; and (4) reared at low altitude and tested in hypoxia without acclimation. We found that mice that developed and were tested at low altitudes had a higher aerobic capacity (both aerobic performance and basal metabolic rate) than those that developed, or were acclimated as adults, at high altitudes. In addition, we found that mice that developed at high altitude did not have a higher aerobic capacity than those that developed at low altitude and were acclimated to high altitude as adults. Both groups tested at high altitudes had higher hematocrits (% red blood cells) and hemoglobin than mice tested at low altitudes. Surprisingly, mice acclimated to low altitudes and given an instantaneous exposure to hypoxia did not suffer a depression in aerobic performance.     

Contribution of shivering and nonshivering thermogenesis to thermogenic capacity for the deer mouse (Peromyscus maniculatus)

Small mammals that are active all year must develop ways to survive the cold winters. Endotherms that experience prolonged cold exposure often increase their thermogenic capacity. Thermogenic capacity incorporates basal metabolic rate (BMR), nonshivering thermogenesis (NST), and shivering thermogenesis (ST). Increasing the capacity of any of these components will result in increased thermogenic capacity. It is often thought that NST should be the most plastic component of thermogenic capacity and as such is the most likely to increase with cold acclimation. We used deer mice to test this hypothesis by acclimating 27 animals to one of two temperatures (5 degrees or 22 degrees C) for 8 wk. We then measured and compared values for thermogenic capacity--BMR, ST, and NST--between the two groups. Thermogenic capacity and NST increased by 21% and 42%, respectively, after cold acclimation. Neither BMR nor ST showed any change after acclimation. Therefore, it appears that deer mice raise their thermogenic capacity in response to prolonged cold by altering NST only.     

Fecal corticosteroids in agouti and non-agouti deer mice (Peromyscus maniculatus)

Total and per gram fecal corticosteroid concentrations were determined for agouti and non-agouti deer mice (Peromyscus maniculatus gracilis) over 24 h under normal caging conditions and after exposure to the stress of novel caging. Per gram corticosteroid concentrations, fecal output, and 24-h corticosteroid production were greater in stressed compared with unstressed deer mice of both color morphs, whereas stressed agoutis had a greater increase in per gram corticosteroid concentrations when compared with non-agoutis. However, due to increased fecal output, stressed non-agouti deer mice had greater 24-h corticosteroid production. Thus, agouti and non-agouti deer mice differ in their hormonal reaction to stress. This is the first demonstration of corticosteroid differences associated with the agouti locus.     

Prediction of Peromyscus maniculatus (deer mouse) population dynamics in Montana, USA, using satellite-driven vegetation productivity and weather data

Deer mice (Peromyscus maniculatus) are the main reservoir host for Sin Nombre virus, the primary etiologic agent of hantavirus pulmonary syndrome in North America. Sequential changes in weather and plant productivity (trophic cascades) have been noted as likely catalysts of deer mouse population irruptions, and monitoring and modeling of these phenomena may allow for development of early-warning systems for disease risk. Relationships among weather variables, satellite-derived vegetation productivity, and deer mouse populations were examined for a grassland site east of the Continental Divide and a sage-steppe site west of the Continental Divide in Montana, USA. We acquired monthly deer mouse population data for mid-1994 through 2007 from long-term study sites maintained for monitoring changes in hantavirus reservoir populations, and we compared these with monthly bioclimatology data from the same period and gross primary productivity data from the Moderate Resolution Imaging Spectroradiometer sensor for 2000-06. We used the Random Forests statistical learning technique to fit a series of predictive models based on temperature, precipitation, and vegetation productivity variables. Although we attempted several iterations of models, including incorporating lag effects and classifying rodent density by seasonal thresholds, our results showed no ability to predict rodent populations using vegetation productivity or weather data. We concluded that trophic cascade connections to rodent population levels may be weaker than originally supposed, may be specific to only certain climatic regions, or may not be detectable using remotely sensed vegetation productivity measures, although weather patterns and vegetation dynamics were positively correlated.