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At least 19 recordsLinked to original sources
PubMed2002

Association of MHC class I and class II gene polymorphisms with vaccine or challenge response to Salmonella enteritidis in young chicks.

Salmonella enteritidis (SE) is a worldwide source of salmonellosis in humans, caused mainly by consumption of contaminated poultry products. The major histocompatibility complex (MHC) class I and class II molecules, which function as antigen-presentation structures, are involved in both macrophage and dendritic cell immune response to Salmonella and may, therefore, play an important role in host resistance to infections. The chicken MHC class I and class II were investigated as candidate genes for immune response to SE. We characterized the complete MHC class I cDNA sequences for an outbred broiler line and four diverse highly inbred lines: two MHC-congenic Leghorn (G-B2 and G-B1), one Egyptian Fayoumi (M15.2), and one Spanish (Sp21.1), to define the allelic sequences within these lines, so that we might study the association between particular MHC polymorphisms and response to SE. The F1 offspring of outbred broiler sires crossed with three inbred lines (G-B1, G-B2, and Fayoumi) were evaluated as young chicks for either bacterial load in spleen and cecum after pathogenic SE inoculation or antibody level after SE vaccination. Alleles defined by a Lys(148)-->Met(148) polymorphism in the MHC class I alpha(2) domain were associated with spleen bacterial load after SE challenge. These results suggest that particular MHC haplotypes may contribute to control of responses to SE, and that particular polymorphisms may serve as markers for genetic resistance to SE in the chicken.

Animals↗
PubMed2003

Genetic susceptibility to vaginal candidiasis.

To enable future studies on host resistance factors and therapy, inbred and outbred mouse strains were tested for susceptibility to vaginal candidiasis. Groups of mice were given 0.5 mg estradiol 3 days before and 4 days after intravaginal challenge with a suspension of Candida albicans. On day 1 after challenge, a swab was used to quantitate infection in all groups and to assure equivalent infection levels. On day 6, this was repeated and the experiment was terminated. BALB/c, the reference strain in repeated experiments, was susceptible, showing persistent infection with levels of cfu at day 6 falling within a range between a twofold decrease and a fourfold increase in relation to day 1 levels. CD-1 outbred mice were markedly resistant, with day 6 cfu levels showing a 74- to 87-fold decrease with respect to day 1 levels, whereas other outbred strains (CF-1, SW, ICR) were susceptible. A BALB/c substrain (ByJ) was also susceptible. With exception of CBA/J, which showed modest resistance, all inbred strains were similarly susceptible, including DBA/2, AKR/J, C3H/HeN, A/J and C57BL/6. The differences between CD-1 and BALB/c mice were also seen with a second C. albicans isolate. Our results show susceptibility to vaginal candidiasis is independent of the major histocompatibility locus H2 haplotype and any effect ascribable to use of particular commercial mouse suppliers. Differences among mouse strains in susceptibility to C. albicans, as seen in previous studies involving nonvaginal challenge routes, are not reflected in this vaginal candidiasis model; in general, such resistance patterns appear specific to the route of challenge administration. The resistance seen in mouse strain CD-1 is of particular interest in that CD-1 is known to be resistant to endocrine disruption by estrogen. Our results suggest this estrogen insensitivity may have broad-ranging effects on processes other than gametogenesis, including vaginal susceptibility to candidiasis.

Animals↗
PubMed2001

Outbreeding increases offspring survival in wild greater horseshoe bats (Rhinolophus ferrumequinum).

The factors influencing the survival of greater horseshoe bat (Rhinolophus ferrumequinum) offspring born over seven years at a maternity colony in south-west Britain were studied. The effects of a range of phenotypic and maternal variables were analysed using a historical data set. In addition, the influence of two genetic measures on mortality, individual heterozygosity and a new measure of outbreeding, termed mean d(2), was assessed. Logistic regressions were undertaken with survival modelled as a binary response variable. Survival to two life stages was studied for each variable and all models were developed for both sexes separately and together. Only one variable, mean d(2), was significantly associated with survival. Male offspring with high mean d(2) scores were more likely to survive to their first and second summers. The influence of mean d(2) was not due to a single locus under selection but a wider multilocus effect and probably represents heterosis as opposed to solely inbreeding depression. Therefore, the extent to which an individual is outbred may determine survival more than widely used phenotypic characteristics such as size and mass. Mean d(2) may reflect immunocompetence, which influences mortality. Protection of mating sites in order to facilitate gene flow and, therefore, outbreeding may help to promote population stability and growth.

Animals↗
PubMed2002

Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 1. Clip design, behavioral outcomes, and histopathology.

In order to take advantage of various genetically manipulated mice available to study the pathophysiology of spinal cord injury (SCI), we adapted an extradural clip compression injury model to the mouse (FEJOTA mouse clip). The dimensions of the modified aneurysm clip blades were customized for application to the mouse spinal cord. Three clips with different springs were made to produce differing magnitudes of closing force (3, 8, and 24 g). The clips were calibrated regularly to ensure that the closing force remained constant. The surgical procedure involved a laminectomy at T3 and T4, followed by extradural application of the clip at this level for 1 min to produce SCI. Three injury severities (3, 8, and 24 g), sham (passage of dissector extradurally at T3-4), and transection control groups were examined (n = 12/group). Quantitative behavioural assessments using the Basso, Beattie, and Bresnahan (BBB; H > 46; df = 4; p < 0.001; Kruskal-Wallis one-way ANOVA) and inclined plane (IP; F = 123; df = 4; p < 0.0001; two-way repeated measures ANOVA) tests showed a significant graded increase in neurological deficits with increasing severity of injury. By day 14, the motor recovery of the mice plateaued. Qualitative examination of the injury site morphology indicated that microcystic cavitation, degenerating axons, and robust astrogliosis were characteristic of the murine response to clip compressive SCI. Morphometric analyses of H&E/Luxol Fast Blue stained sections at every 50 microm from the injury epicenter indicated that with greater injury severity there was a progressive decrease in residual tissue (F = 220, df = 3; p < 0.0001; two-way ANOVA). In addition, statistically significant differences were found in the amount of residual tissue at the injury epicenter between all of the injury severities (p < 0.05, SNK test). This novel, graded compressive model of SCI will facilitate future studies of the pathological mechanisms of SCI using transgenic and knockout murine systems.

Animals↗
PubMed2002

Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice.

Behavioral tests, tightrope success, and exploratory activity in a T maze were conducted with male and female mice for 65 wk. Four groups were defined: the lower performance slow males and slow females and the higher performance fast males and fast females. Fast females showed the longest life span and the highest performance, and slow males showed the lowest performance and the shortest life span. Oxidative stress and mitochondrial electron transfer activities were determined in brain of young (28 wk), adult (52 wk), and old (72 wk) mice in a cross-sectional study. Brain thiobarbituric acid reactive substances (TBARS) were increased by 50% in old mice and were approximately 15% higher in males than in females and in slow than in fast mice. Brain Cu,Zn-superoxide dismutase (SOD) activity was increased by 52% and Mn-SOD by 108% in old mice. The activities of mitochondrial enzymes NADH-cytochrome c reductase, cytochrome oxidase, and citrate synthase were decreased by 14-58% in old animals. The cumulative toxic effects of oxyradicals are considered the molecular mechanism of the behavioral deficits observed on aging.

Aging↗
PubMed2000

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol.

Injectable anaesthetics are widely used to anaesthetize rats, but recovery times are often prolonged. Reversible anaesthetic regimens have the advantage that animals may be recovered quickly, thus reducing the incidence of postoperative complications such as hypothermia, and also providing a means of treating inadvertent anaesthetic overdose. This study assessed and compared the characteristics of anaesthesia induced with combinations of sufentanil and medetomidine administered as a single subcutaneous or intraperitoneal dose, and reversal with butorphanol and atipamezole. Combinations of sufentanil/medetomidine at 40 microg/150 microg and 50 microg/150 microg/kg administered subcutaneously, and 80 microg/300 microg/kg by intraperitoneal injection were found to produce surgical anaesthesia for 101+/-49, 124+/-45 and 76+/-23 min (means +/- SD) respectively. All three combinations produced marked respiratory depression 30 min after injection (< 50% of resting respiratory rate). Oxygen saturation, measured by pulse oximetry, was < 50% in all groups 30 min following drug administration. Subcutaneous administration is recommended since it resulted in a more reliable and more rapid induction of anaesthesia than intraperitoneal administration. The administration of butorphanol and atipamezole (0.2/0.5 mg/kg s.c.) resulted in a rapid (< 7 min) reversal of anaesthesia and an associated respiratory depression. The induction of anaesthesia with sufentanil/medetomidine and its reversal with a combination of atipamezole and butorphanol is an effective technique for anaesthetizing rats. However, due to the marked respiratory depression and the resulting hypoxia, we recommend that this regimen should only be used in animals which are free from respiratory disease and that oxygen should be provided during anaesthesia.

Anesthesia↗
PubMed2000

Dynamics of the recovery period in rats exposed to global cerebral ischemia.

Global cerebral ischemia-reperfusion was modeled by thermocoagulation of the vertebrobasilar arteries followed by occlusion of both carotid arteries. Behavioral parameters, neurological status, and mnesic functions in rats were studied during the recovery period. It is concluded that this model of ischemia is reproducible and can be used for studying ischemia-reperfusion damages to the brain.

Animals↗
PubMed1974

Alloantiserum-induced inhibition of immune response gene product function. II. Genetic analysis of target antigens.

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F(1) T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA(+)2(+), but the serum had little if any effect on the GA response of T cells from GA(+)2(-) animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA(+)2(-) outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F(1), while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA(+)2(+) outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.

Antibody Formation↗
PubMed2002

Sodium bicarbonate enhances the severity of infection in neutropenic mice orally inoculated with Listeria monocytogenes EGD.

Epidemiological studies have suggested an association between antacid therapy and development of listeriosis in humans. In this study we used a neutropenic mouse model to demonstrate that oral administration of sodium bicarbonate shortly before intragastric (i.g.) inoculation with Listeria monocytogenes EGD (serotype 1/2a) significantly increased the severity of the resulting systemic infection. An explanation for this observation is provided by evidence that L. monocytogenes EGD is rapidly inactivated in synthetic gastric fluid at pH below 5. A second strain of L. monocytogenes (CM [serotype 1/2b]) exhibited little ability to cause systemic infection following i.g. inoculation and was not significantly enhanced by administration of sodium bicarbonate. Strain CM was readily inactivated in synthetic gastric fluid even at pH 7. These data suggest that gastric acidity and enzymes provide some innate defense against gastrointestinal listeriosis in neutropenic mice.

Animals↗
PubMed2002

Rosmarinic acid and caffeic acid reduce the defensive freezing behavior of mice exposed to conditioned fear stress.

RATIONALE: We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) and its major metabolite caffeic acid have antidepressive-like activity in the forced swimming test. OBJECTIVE: The present study was designed to examine whether rosmarinic acid and caffeic acid might also be effective in other types of stress model. METHODS: The conditioned fear stress paradigm was used as a stress model for assessing the effects of rosmarinic acid and caffeic acid. RESULTS: Rosmarinic acid (0.25-4 mg/kg, IP) induced a dose-dependent, U-shaped reduction in the duration of the defensive freezing behavior of mice exposed to conditioned fear stress. Caffeic acid (1-8 mg/kg, IP) also dose-dependently reduced this freezing behavior. However, neither substance, at doses that produced a significant reduction in the freezing behavior, affected spontaneous motor activity. CONCLUSIONS: These results confirm that rosmarinic acid and caffeic acid may inhibit the emotional abnormality produced by stress.

Analysis of Variance↗
PubMed2001

Some factors influencing transmission of toxoplasma in pregnant rats fed cysts.

An overall 44% transplacental transmission rate was observed in 221 rats fed cysts of 12 Toxoplasma strains at 15 days of pregnancy, with a range of 0-90% transmission. Considerable variability in the transmission rate was seen among different groups of rats that received similar Toxoplasma inocula; this is attributed to genetically based susceptibility to Toxoplasma among individuals of the outbred Wistar strain of rats. Transplacental transmission was more frequent in Long Evans than in Wistar rats. Significant differences in the rate of transmission were not found between rats that were fed similar Toxoplasma inocula 6-8 days or 15 days after conception. The frequency of transmission was not affected by the strain or dose of Toxoplasma used.

Animals↗
PubMed2002

Neuronal storage of histamine in the brain and tele-methylimidazoleacetic acid excretion in portocaval shunted rats.

Rats with portocaval anastomosis (PCA), an animal model of hepatic encephalopathy (HE), have very high brain histamine concentrations. Our previous studies based on a biochemical approach indicated histamine accumulation in the neuronal compartment. In this study, immunohistochemical evidence is presented which further supports the amine localization in histaminergic neurons. These neurons become pathological in appearance with cisternae frequently seen along histaminergic fibres in many brain areas, including the hypothalamus, amygdala, substantia nigra and cerebral cortex. Such formations were not observed in sham-operated animals. The neuronal deposition is predominant, and unique for histamine. It serves as a mechanism to counterbalance excessive brain neurotransmitter formation evoked by PCA. However, there are other mechanisms. The data provided here show that there is also a significant increase in histamine catabolism in the shunted rats, as reflected by both the higher brain N-tele-methylhistamine (t-MeHA) concentration and urinary excretion of N-tele-methylimidazoleacetic acid (t-MelmAA), a major brain histamine end product. The stomach, in addition to the brain, is a site of enhanced histamine synthesis in portocavally shunted subjects. After gastrectomy or food deprivation to eliminate the contribution of the stomach, shunted rats excrete significantly more t-MelmAA, implying the role of the CNS. This last finding suggests that under strictly defined conditions, namely in parenterally fed HE patients with abnormal plasma L-histidine, the measurement of urinary t-MelmAA might provide valuable information concerning putative brain histaminergic activity.

Animals↗
PubMed2001

Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci.

Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and susceptibility to skin carcinogenesis respectively, show significant linkage disequilibrium (LD) at genetic markers mapping on chromosomal regions where skin cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively) have been mapped in standard crosses. Analysis of these regions for genetic linkage with skin cancer phenotypes in 245 (Car-R x Car-S)F2 intercross mice, by using single nucleotide polymorphisms (SNPs), revealed significant linkage at a possible allelic form of the Skts1 locus, whose mapping region was shortened to a <5.5-cM interval near the Tyr locus. The Car-derived Skts1 locus was linked with papilloma multiplicity and latency by a recessive inheritance of the susceptibility allele. Putative loci on Chr 5 (Skts3) and 9 (Psl1) showed no significant linkage. These results point to the important role of the Stks1 locus in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes.

Animals↗
PubMed2001

Confounding factors in toxicity testing.

The necessity for understanding normal human functions and the mechanisms which underlie dysfunction in these processes is essential in the promotion of a healthier lifestyle. To achieve this goal utilization of a suitable animal model is necessary in order to develop new pharmaceutical agents to alleviate diseases or chemicals to enhance the quality of life. It is incumbent upon investigators to choose a species in which pharmacokinetic principles are established and it is important that these phenomena resemble those of the humans. The choice of rats has specific advantages in that these rodents possess similar pharmacodynamic parameters to humans. Other advantages include availability, low cost, ease of breeding, and an extensive literature data-base to enable comparisons to present findings. However, in the interpretation of data from animals to humans, there are factors which need to be recognized as playing important roles in chemical-induced outcomes. The confounding factors include strain, supplier, age, gender, hormonal status and dietary intake. The aim of this article is to demonstrate that there are differences in the responsiveness of rat stock/strains to chemicals and that lack of consideration of confounding factors yields inappropriate conclusions regarding risk assessment for humans.

Age Factors↗
PubMed2001

Comparison of arterial blood pressure in different strains of mice.

The present study was performed to compare the resting level of arterial blood pressure when monitored for 24 h/day in outbred Swiss Webster (SW) and inbred C57BL/ 6J, A/J, C3HeB/FeJ, and SWR/J mice. Mean arterial pressure (MAP) and heart rate (HR) varied throughout the day, with maximal values observed in the hours of darkness. Systolic (SAP), MAP, and diastolic (DAP) arterial blood pressure averaged 122 +/- 2, 112 +/- 2, and 102 +/- 2 mm Hg, respectively, in conscious SW mice (N = 6). No differences were detected in the 24-h averages of MAP between SW, C57BL/6J (N = 7), A/J (N = 5), C3HeB/FeJ (N = 5), or SWR/J (N = 7) mice maintained on a normal sodium diet. Average daily heart rate (HR) was highest in the C3HeB/FeJ (665 +/- 15 beats/min) and lowest in the C57BL/6J (594 +/- 9 beats/min). The MAP was significantly increased in SW mice administered L-NAME (133 +/- 2 mm Hg, N = 5) and significantly decreased in SW mice administered captopril (99 +/- 2 mm Hg, N = 5). These studies demonstrate similar levels of resting arterial pressure in different mouse strains under baseline conditions.

Animals↗
PubMed2002

Differences in brain area concentrations of dopamine and serotonin in Myers' High Ethanol Preferring (mHEP) and outbred rats.

Both male and female mHEP rats consume excessive amounts of ethanol and thus offer a rational model for examining biochemical and behavioral differences with non-drinking rat lines. Differences in basal concentrations of 5-hydroxytryptamine (5-HT) and dopamine (DA) correlate with the consumption of ethanol in some ethanol-preferring rat lines. The concentrations of 5-HT and DA were examined by HPLC in five brain areas (prefrontal cortex, hippocampus, nucleus accumbens, striatum and hypothalamus) of ethanol-näive rats and after the oral administration of 0.25 or 1.0 g ethanol/kg in the male and female mHEP rat, the male Wistar rat, and the female Sprague-Dawley rat. The mHEP and control rats that received ethanol were screened for drinking in a 10-day "step-up" 3% to 30% ethanol solutions beginning at postnatal days 40 and 80, and then tested at 150 days of age. The levels of DOPAC in females were lower in the hippocampus of both naïve mHEP and ethanol-treated Sprague-Dawley rats. In striatum, the concentrations of 5-HT and DA were elevated in both mHEP and ethanol-treated Sprague-Dawley female rats. The concentrations of 5-HT and its metabolite, 5-HIAA, were lower in the nucleus accumbens of the ethanol-näive female mHEP rat relative to the female outbred control. In the male rats, the levels of DA, HVA and DOPAC, as well as 5-HT and 5-HIAA were reduced in the hypothalamus of both ethanol-näive mHEP rats and Wistar rats receiving ethanol by gavage. These data demonstrate differences in neurotransmitter activity between the selectively bred mHEP rat and the outbred rat strains. There are few common features found in both the male and the female mHEP rat when compared to their respective controls. Differences in neurotransmitter function in these brain areas may account for some of the behavioral differences previously demonstrated between the two sexes of the mHEP rat.

Alcohol-Induced Disorders, Nervous System↗
PubMed2003

Differential sensitivity to acute administration of Ritalin, apomorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior.

RATIONALE: Previous studies of mice ( Mus domesticus) selectively bred for high voluntary wheel running have suggested that the hyperactivity is associated with dysfunction in the dopaminergic neuromodulatory system and that high-running mice may represent a useful genetic model for attention deficit hyperactivity disorder (ADHD). OBJECTIVES: We tested the hypothesis that mice from the four replicate hyperactive lines would respond differently to methylphenidate (Ritalin), apomorphine (non-selective dopamine agonist), SCH 23390 (selective D1-like dopamine antagonist), and raclopride (selective D2-like dopamine antagonist) than individuals from the four replicate, randomly bred, control lines. METHODS: After animals were habituated (3 weeks) to their cages with attached wheels, drugs were administered via intraperitoneal injections, at night, during peak wheel-running activity. Revolutions on wheels 10-70 min post-injection were used to quantify drug responses. RESULTS: Ritalin (15 mg/kg and 30 mg/kg) increased wheel running in control lines but decreased running in selected lines. A low-dose (0.125 mg/kg) of apomorphine reduced wheel running by a similar amount in control and selected lines; however, higher doses of apomorphine (0.25 mg/kg and 0.5 mg/kg) produced greater reductions in wheel running in the control lines. SCH 23390 (0.025, 0.05, and 0.1 mg/kg) caused greater reductions in wheel running in control than in selected lines. Raclopride (0.5, 1, and 2 mg/kg) reduced wheel running by a similar amount in control and selected lines. CONCLUSIONS: These results support the interpretation that genetically determined hyperactive wheel-running behavior is associated with altered dopaminergic function in this mouse model. More specifically, results suggest that D1-like (D1 or D5), but not D2-like (D2, D3, or D4), dopamine receptors have reduced function in the high-running mice. The fact that Ritalin decreased wheel running in selected lines further supports their use as an animal model of ADHD.

Animals↗