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Hypothyroidism in reproductively inhibited prairie deer mice (Peromyscus maniculatus bairdi) from laboratory populations.

Several thyroid function parameters were compared between reproductively inhibited prairie deer mice of both sexes taken from laboratory populations and corresponding reproductively capable controls. The results of these experiments indicated the following: 1) prairie deer mice females had a statistically significant daily variation in mean serum thyroxine concentration and males displayed a similar trend; 2) total serum thyroxine and triiodothyronine were significantly lower in both male and female reproductively inhibited population animals compared with reproductively capable controls; 3) several morphometric characteristics of the thyroid of male and female population prairie deer mice were significantly different from that of control males and females, suggesting functional hypothyroidism in both sexes; 4) thyroid histology of male population deer mice was different from that of female population animals. In males, the data suggested that thyroid-stimulating hormone (TSH) stimulation was deficient due to some undetermined secondary hypothyroidism. In females, reduced serum thyroxine and triiodothyronine concentrations were observed due to primary hypothyroidism of unknown origin. The interrelationship between thyroid and adrenal function is discussed here and it is concluded that each of the systems may contribute to the observed reproductive inhibition. In particular, it was noted that the mechanism of response between population males and females may be quite different. No conclusive data are available to suggest whether one or the other system is the primary controller of the reproductive inhibition.

Animals↗

Oxidoreduction of butanol in deermice (Peromyscus maniculatus) lacking hepatic cytosolic alcohol dehydrogenase.

In view of conflicting information in the literature regarding enzyme systems responsible for alcohol oxidation in deermice previously reported to lack hepatic alcohol dehydrogenase (ADH) activity, the reversibility of butanol oxidation was studied in vivo and in liver-perfusion systems. Mixtures of [1,1-2H2]ethanol and butanol were given intraperitoneally to deermice lacking (ADH-) or possessing (ADH+) ADH activity, followed by analysis of alcohols in blood by GC/MS. 2H exchange between the two alcohols was seen in all experiments. In ADH- deermice, the 2H excess of butanol increased steadily and reached 18 +/- 5% after 2.5 h. In ADH+ deermice, butanol was rapidly eliminated and the 2H excess was about 7% after 0.5 h. In similar experiments with rats, the 2H excess was about 40% for 2 h. Perfusions of livers from ADH- deermice with mixtures of unlabelled and 1-[2H]butanol showed significant but slow intermolecular hydrogen transfer at C1, indicating oxidoreduction catalyzed by a dehydrogenase. Slow reduction of butanal was observed in mitochondria from ADH- deermice. ADH activity with a pH optimum of 10 and Km for ethanol of 6 mM was detected in the inner mitochondrial membranes from rats and deermice. However, low rates of oxidation observed in experiments carried out with perfused livers and in vitro suggest that this enzyme system does not contribute significantly to alcohol oxidation in vivo. Thus, perfused liver from ADH- deermice appears to be a useful system for studies of ADH-independent oxidation of alcohols. The 2H exchange between the alcohols seen in vivo indicates that both ethanol and butanol are substrates for a common extrahepatic dehydrogenase in ADH- deermice.

Alcohol Dehydrogenase↗

Immunity reduces reservoir host competence of Peromyscus leucopus for Ehrlichia phagocytophila.

Infection with Ehrlichia phagocytophila in white-footed mice is transient and followed by a strong immune response. We investigated whether the presence of acquired immunity against E. phagocytophila precludes white-footed mice from further maintenance of this agent in nature. Mice were infected with E. phagocytophila via tick bite and challenged either 12 or 16 weeks later by Ixodes scapularis nymphs infected with the same agent. Xenodiagnostic larvae fed upon each mouse simultaneously with challenging nymphs and 1 week thereafter. Ticks were tested for the agent by PCR, and the prevalence of infection was compared to that in ticks that fed upon nonimmune control mice. Only 30% of immunized mice sustained cofeeding transmission of E. phagocytophila between simultaneously feeding infected and uninfected ticks, compared to 100% of control mice. An average of 6.3% of xenodiagnostic ticks acquired Ehrlichia from previously immunized mice when fed 1 week after the challenge, compared to 82.5% infection in the control group. Although an immune response to a single infection with E. phagocytophila in white-footed mice provided only partial protection against reinfection with the same agent, the majority of mice were rendered reservoir incompetent for at least 12 to 16 weeks. Immunity acquired by mice during I. scapularis nymphal activity in early summer may exclude a large proportion of the mouse population from maintaining E. phagocytophila during the period of larval activity later in the season.

Animals↗

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 naïve 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 naïve 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.

Animals↗

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.

Animals↗

Pathogenesis of Trypanosoma brucei infection in deer mice (Peromyscus maniculatus). V. Macrophage ultrastructure and function.

Macrophage numbers increased in the spleen, liver, testes, heart, and kidney of deer mice infected for seven to ten weeks with Trypanosoma brucei EATRO 110. The macrophages were activated as indicated by their increased size and significant increases in numbers of cell organelles including profiles of rough endoplasmic reticulum (which also increased in length), mitochondria, primary and secondary lysosomes, bundles of Golgi's apparatus, and free lysosomes compared to macrophages from control mice. Some macrophages representing epithelioid cells have even greater numbers of organelles than the activated macrophages and had interdigitation in some locations, such as the heart, but with minimal phagocytic activity. These epithelioid cells were present in the kidney, testes, and particularly in the heart of infected mice. Few cardiac macrophages had finely granular deposits on their nuclear membrane. The activated macrophages had enhanced phagocytosis of trypanosomes, red blood cells, neutrophils, eosinophils, lymphocytes, and plasma cells. In addition to phagocytosis, another probable consequence of macrophage activation may be depression of lymphocyte function. Phagocytosis of trypanosomes by neutrophils also was encountered occasionally.

Animals↗

Testicular apoptosis is down-regulated during spontaneous recrudescence in white-footed mice (Peromyscus leucopus).

Among individuals of many nontropical species, seasonal breeding is timed by tracking changes in the daily photoperiod. Transfer of rodents to short (< 12 h of light/day) day lengths for 6 to 14 weeks can induce regression of the testes mediated by apoptosis. After 16 to 20 weeks of short day exposure, reproductive function is "spontaneously" initiated, and testicular recrudescence is observed. The gonadal mechanisms that underlie testicular recrudescence are not fully understood. If the onset of testicular regrowth that occurs during spontaneous recrudescence reflects a down-regulation of apoptotic signals, then a decline in apoptosis should be noted concurrent with increased testis mass. This experiment sought to assess the role of apoptosis in the restoration of reproductive capacity to photoperiod-inhibited white-footed mice. Males were assigned to long (16:8 LD) or short (8:16 LD) photoperiods for 0, 14, 18, 22, 26, or 30 weeks. At each of these time points, testis mass and testosterone concentrations were assessed. In addition, apoptotic activity was measured using both in situ terminal deoxynucleotidyl transferase dNTP end labeling (TUNEL) and DNA laddering. Short photoperiod exposure induced maximal decreases in testicular parameters after 14 weeks (p < 0.05). After 26 weeks of short days, testis mass was no longer different between males housed in long days and those housed in short days. In contrast, the high incidence of apoptotic TUNEL labeling and DNA laddering observed at 14 weeks was reduced to long day values after 22 weeks of short day exposure. Together, our results establish that a decrease in testicular apoptosis coincides with testicular recrudescence in white-footed mice. The current study demonstrates a decline in the incidence of testicular cell death concomitant with changes in testis mass or length, elucidating a timeline of changes at the cellular level related to the onset of recrudescence.

Animals↗

Effect of transatlantic transport on reproduction of agouti and nonagouti deer mice, Peromyscus maniculatus.

In conjunction with establishing colonies of deer mice in the UK, effects of transportation on reproduction in agouti (A) and nonagouti (a) deer mice were assessed. Adults were shipped via ground courier and air freight from Northampton, Massachusetts, USA to Sutton Bonington, Leicestershire, England in February and June. Deer mice were paired upon arrival in Sutton Bonington, whereas matched controls were paired in the original colonies at shipping. To assess reproduction, the following variables were monitored for 110 days for all 96 pairs: number of pairs producing litters, time from pairing to birth, interlitter interval, litter size at birth, and litter size at weaning. Generally, shipping suppressed litter production and delayed its timing, but had less effect on litter size. Overall, 32 of 48 control pairs (67%) produced 69 litters compared with 37 litters from 21 of 48 pairs (44%) after shipping. Pairing-to-first-litter intervals were approximately two oestrous cycles shorter in control animals (39 vs 53 days). Averaged over all litters, litter size was higher in control pairs (4.4 vs 4.0). With respect to genotype, control agouti deer mice were less productive than nonagouti animals, but they reproduced better than nonagoutis after shipping. In control animals, colourmorphs did not differ with respect to litter production or timing, but agouti pairs had smaller litters (first litter: A: 3.1, a: 4.2) and this difference increased at successive litters (third litter A: 3.9, a: 6.0). After shipping, agouti animals produced more litters (A: 22, a: 15), and did so earlier (pairing to birth: A: 47 days, a: 60 days), as well as more frequently (interlitter interval: A: 32 days, a: 51 days). Litter size was also more similar between genotypes after shipping (A: 4.0, a: 4.1). Overall, control agouti animals produced 37% fewer offspring than nonagouti pairs. (A: 116 neonates, a: 185 neonates), but after shipping agouti deer mice produced 43% more offspring than nonagouti animals (A: 87 neonates, a: 61 neonates). In sum, transport stress suppressed reproduction for several weeks after shipping and this suppression was exacerbated in nonagouti deer mice.

Agouti Signaling Protein↗