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1.
Exp Anim ; 66(4): 321-327, 2017 Oct 30.
Article in English | MEDLINE | ID: mdl-28626157

ABSTRACT

Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.


Subject(s)
Animals, Laboratory/physiology , Body Temperature Regulation/physiology , Diet, Protein-Restricted , Dietary Proteins/administration & dosage , Mice, Inbred ICR/metabolism , Mice, Inbred ICR/physiology , Torpor/physiology , Animals , Body Weight , Energy Metabolism/physiology , Female
2.
J Am Assoc Lab Anim Sci ; 52(5): 524-30, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24041205

ABSTRACT

During pregnancy, women often show a willingness to make positive lifestyle changes, such as smoking cessation, initiation of a vitamin regimen, improvement of their diet, and increases in their levels of exercise or physical activity. To study health outcomes in both pregnant mice and their offspring, we developed a model of controlled maternal exercise during mouse pregnancy. Female ICR and C57BL/6 mice underwent controlled wheel walking for 1 h daily, 5 d each week, at a speed of 6 m/min prior to and during pregnancy and nursing. Dam body weight, food consumption, pregnancy rates, litter size, pup weights and litter survival were used as markers of pregnancy success and were not significantly affected by controlled maternal exercise. The proposed exercise paradigm is a safe pregnancy intervention and can be explored further.


Subject(s)
Mice, Inbred C57BL/physiology , Mice, Inbred ICR/physiology , Motor Activity/physiology , Physical Conditioning, Animal/physiology , Pregnancy, Animal/physiology , Animals , Body Weight/physiology , Eating/physiology , Female , Humans , Lactation/physiology , Litter Size , Mice , Models, Animal , Pregnancy , Species Specificity
3.
Anim Sci J ; 84(6): 502-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23607774

ABSTRACT

Thirty-one ICR pregnant mice were assigned to a control or a potassium chloride (KCl) diet group to clarify the effects of KCl supplementation on water intake, bodyweight gains and serum components in pregnant and lactating mice, and 5% KCl was supplemented in KCl diets from 6.5 days post coitus to 1 or 14 days after parturition. Feed intake was not affected by treatment, but supplemental KCl decreased bodyweight gains of lactating mice and their neonatal mice. Water intake and urine volume of KCl supplemented mice were significantly higher than those of control mice during pregnancy and supplemental KCl decreased serum urea N in pregnant mice. Supplemental KCl increased water intake drastically in lactating mice immediately after parturition and increased serum K at 14 days after parturition. Histological alteration using hematoxylin-eosin was not found in the kidney of each mouse at 1 or 14 days after parturition. These results indicate that high KCl supplementation accelerates water intake in lactating mice and prevents bodyweight gains of maternal and neonatal mice during lactation.


Subject(s)
Drinking/physiology , Mice, Inbred ICR/physiology , Potassium Chloride/administration & dosage , Pregnancy, Animal/physiology , Weight Gain/physiology , Animals , Animals, Newborn , Dietary Supplements , Female , Mice , Mice, Inbred ICR/blood , Mice, Inbred ICR/urine , Pregnancy , Weight Gain/drug effects
4.
J Am Assoc Lab Anim Sci ; 51(4): 407-11, 2012 Jul.
Article in English | MEDLINE | ID: mdl-23043805

ABSTRACT

Stereotypic behaviors are repetitive invariant behaviors that are common in many captive species and potentially indicate compromised welfare and suitability as research subjects. Adult laboratory mice commonly perform stereotypic bar-gnawing, route-tracing, and back-flipping, although great individual variation in frequency occurs. Early life factors (for example, level of maternal care received) have lasting effects on CNS functioning and abilities to cope with stress and therefore may also affect stereotypic behavior in offspring. Access to maternal resources and care are influenced by the number of pups in a litter; therefore, we examined both litter size and its potential correlate, weight at weaning, as early environmental predictors of adult stereotypic behavior in laboratory mice. Further, we assessed the effects on offspring stereotypic behavior of delaying the separation of mother and pups (weaning) beyond the standard 21 d of age. Analyzing stereotypic behavior in 3 different mouse colonies composed of 2 inbred strains (C57BL/6N and C57BL/6J) and an outbred stock (CD1[ICR]) revealed significant positive correlation between litter size and stereotypic behavior in female, but not male, mice. Weight and age at weaning did not significantly affect levels of stereotypy in either sex. Litter size therefore may be a useful indicator of individual predisposition to stereotypic behavior in female laboratory mice.


Subject(s)
Behavior, Animal/physiology , Litter Size/physiology , Mice, Inbred C57BL/physiology , Mice, Inbred ICR/physiology , Stereotyped Behavior/physiology , Animals , Body Weight , Female , Male , Mice , Sex Characteristics , Weaning
5.
J Mol Neurosci ; 46(2): 276-84, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21598024

ABSTRACT

The use of mice as experimental models in pharmacological and biochemical research began over 100 years ago, during which time different mice strains with specific features were developed. Numerous studies demonstrate that the pharmacological efficacy of various compounds significantly varies among different animal strains, a factor which must be considered when analyzing experimental data. The Sabra strain, developed more than 35 years ago, is widely used for research in Israel but has an unclear origin and is not characterized as well as other strains. Comparative analyses of the molecular characteristics of Sabra and other strains should help to understand their characteristics and to enhance the validity of their experimental use. Thus, four mouse strains-outbred ICR and Sabra as well as inbred C57Bl/6J and Balb/c were compared. Animals' weight, blood corticosterone and hippocampal BDNF mRNA levels were measured, and animals' behavior was compared using the EPM, open field, FST, and hot plate tests. We found that although Sabra mice are bigger and heavier than other tested lines, this is not reflected in behavior or in biomolecular features, wherein Sabra mice lay within the diapason of other tested animals. Thus, behavioral tests of anxiety-like behavior and locomotor activity revealed that Sabra mice scored close to the mean of all tested lines. Analysis of blood corticosterone levels did not show significant differences among tested strains. We also found a correlation between general and locomotor activity of the tested strains and their hippocampal BDNF mRNA expression. In summary, we may conclude that Sabra mice have traits similar to the better known lines, and therefore they are good subjects for neuroscience research.


Subject(s)
Mice/physiology , Animals , Animals, Outbred Strains/genetics , Animals, Outbred Strains/physiology , Animals, Outbred Strains/psychology , Anxiety/genetics , Anxiety/physiopathology , Body Weight/physiology , Brain-Derived Neurotrophic Factor/analysis , Brain-Derived Neurotrophic Factor/genetics , Corticosterone/blood , Exploratory Behavior/physiology , Hippocampus/chemistry , Hot Temperature , Locomotion/physiology , Male , Maze Learning/physiology , Mice/genetics , Mice/psychology , Mice, Inbred BALB C/genetics , Mice, Inbred BALB C/physiology , Mice, Inbred BALB C/psychology , Mice, Inbred C57BL/genetics , Mice, Inbred C57BL/physiology , Mice, Inbred C57BL/psychology , Mice, Inbred ICR/genetics , Mice, Inbred ICR/physiology , Mice, Inbred ICR/psychology , Motor Activity/physiology , Pain Threshold/physiology , Physical Endurance/physiology , RNA, Messenger/analysis , Swimming
6.
Biol Lett ; 6(1): 132-5, 2010 Feb 23.
Article in English | MEDLINE | ID: mdl-19710051

ABSTRACT

Many animal species employ natural hypothermia in seasonal (hibernation) and daily (torpor) strategies to save energy. Facultative daily torpor is a typical response to fluctuations in food availability, but the relationship between environmental quality, foraging behaviour and torpor responses is poorly understood. We studied body temperature responses of outbred ICR (CD-1) mice exposed to different food reward schedules, simulating variation in habitat quality. Our main comparison was between female mice exposed to low foraging-cost environments and high-cost environments. As controls, we pair-fed a group of inactive animals (no-cost treatment) the same amount of pellets as high-cost animals. Mice faced with high foraging costs were more likely to employ torpor than mice exposed to low foraging costs, or no-cost controls (100% versus 40% and 33% of animals, respectively). While resting-phase temperature showed a non-significant decrease in high-cost animals, torpor was not associated with depressions in active-phase body temperature. These results demonstrate (i) that mice show daily torpor in response to poor foraging conditions; (ii) that torpor incidence is not attributable to food restriction alone; and (iii) that high levels of nocturnal activity do not preclude the use of daily torpor as an energy-saving strategy. The finding that daily torpor is not restricted to conditions of severe starvation puts torpor in mice in a more fundamental ecological context.


Subject(s)
Appetitive Behavior/physiology , Body Temperature Regulation/physiology , Circadian Rhythm/physiology , Energy Metabolism/physiology , Mice, Inbred ICR/physiology , Animals , Body Temperature , Ecosystem , Female , Linear Models , Mice
7.
Exp Anim ; 57(1): 19-25, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18256515

ABSTRACT

The present study was conducted to elucidate the susceptibility of embryos and fetuses at different gestational stages to the maternal stress in mice. Groups of pregnant ICR mice were subjected to daily 12-h restraint stress, taped in the supine position on a plastic board, on gestational days (GD) 1-4, 5-8, 9-12 and 13-16, respectively. Caesarean sections were performed on gestational day 18, and the fetuses were weighed and examined for morphological defects. During the daily restraint for 4 days, the maternal body weights markedly decreased. Although the body weights recovered gradually after termination of the stress, the recovery was not full until the final stage of pregnancy. Interestingly, restraint stress caused growth retardation of the fetuses, leading to a significant decrease in their body weights, and increased early and late resorptions of embryos and fetuses according to the stress periods. Although the preceding (GD1-4) and concurrent (GD5-8) stresses did not affect embryonic implantation, restraint stress on GD9-12 caused cleft palate. Whereas vertebral abnormalities, mainly bipartite ossification, were observed only in animals stressed on GD5-8, abnormalities of sternebrae, exhibiting asymmetric or bipartite ossification, were enhanced by the stress at all of the gestational stages. On the other hand, the incidence of other malformations including renal malposition and costal abnormalities was not increased by stress at any of the 4 stages. Taken together, the results suggest that intensive restraint stress influences the maternal body weight resulting in growth retardation and increased mortality of embryos and fetuses, in addition to gestational stage-specific ventricular dilatation, cleft palate and sternal abnormalities.


Subject(s)
Fetal Development/physiology , Mice, Inbred ICR/physiology , Restraint, Physical/physiology , Animals , Body Weight/physiology , Cleft Palate/etiology , Cleft Palate/veterinary , Female , Fetal Growth Retardation/veterinary , Gestational Age , Mice , Pregnancy , Rodent Diseases , Spine/abnormalities
8.
Physiol Biochem Zool ; 80(1): 146-56, 2007.
Article in English | MEDLINE | ID: mdl-17160887

ABSTRACT

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate.


Subject(s)
Corticosterone/blood , Mice, Inbred ICR/physiology , Motor Activity , Stress, Physiological , Adrenal Glands/anatomy & histology , Animals , Body Size , Body Weight , Corticosterone/physiology , Crosses, Genetic , Female , Male , Mice , Mice, Inbred ICR/blood , Mice, Inbred ICR/genetics , Motor Activity/genetics , Motor Activity/physiology , Restraint, Physical , Sex Characteristics , Species Specificity , Stress, Physiological/genetics
9.
Lab Anim ; 38(2): 169-77, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15070457

ABSTRACT

In socially unstable groups of male laboratory mice, individuals may experience a chronic stress situation. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning, and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study, the combined effect of these husbandry procedures were tested for their long-term effect on stress in groups of moderately aggressive (BALB/c) and severely aggressive (CD-1) male mice. The physiological and behavioural stress-related parameters used were body weight, food and water intake, spleen and thymus weight, adrenal tyrosine hydroxylase activity, urine corticosterone levels and behaviour in a cage emergence test. Long-term provision of nesting material and its transfer during cage cleaning was found to influence several stress-related physiological parameters. Mice housed in cages enriched with nesting material had lower urine corticosterone levels and heavier thymuses, and they consumed less food and water than standard-housed mice. Furthermore, marked differences were found between strains. CD-1 mice were less anxious in the cage emergence test, weighed more, ate and drank more, and had heavier thymuses but lighter spleens and lower corticosterone levels than BALB/c mice. We conclude that the long-term provision of nesting material, including the transfer of nesting material during cage cleaning, reduces stress and thereby enhances the welfare of laboratory mice.


Subject(s)
Agonistic Behavior/physiology , Animal Husbandry/methods , Behavior, Animal/physiology , Mice, Inbred BALB C/psychology , Mice, Inbred ICR/psychology , Social Dominance , Stress, Psychological/psychology , Animals , Body Weight/physiology , Corticosterone/urine , Creatinine/urine , Drinking/physiology , Eating/physiology , Eating/psychology , Male , Mice , Mice, Inbred BALB C/physiology , Mice, Inbred ICR/physiology , Organ Size , Random Allocation , Spleen/physiology , Stress, Psychological/etiology , Thymus Gland/physiology , Tyrosine 3-Monooxygenase/metabolism
10.
J Anim Sci ; 81(10): 2562-7, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14552384

ABSTRACT

In previous work, a mouse line selected for resistance (R) to fescue toxicosis had higher activities of two hepatic Phase II detoxification enzymes than a mouse line selected for fescue toxicosis susceptibility (S). The primary objective of the present study was to determine whether those same lines also differed in hepatic Phase I enzyme activity, estimated from sleep time (ST) following sodium pentobarbital anesthesia. Additional objectives were to determine whether ST differences between lines were modulated by endophyte-infected fescue in the diet (with or without an enzyme inducer) and whether ST of individual mice was correlated with the effect of a toxin-containing diet on the postweaning growth of those mice. In Exp. I, 24 males from each line were randomly assigned to each of five diets: control (commercial rodent food meal); E+ (50% endophyte-infected fescue seed, 50% control); E+P (the E+ diet supplemented with 1,000 ppm phenobarbital); E- (50% endophyte-free fescue seed, 50% control); and E-P (the E- diet supplemented with 1,000 ppm phenobarbital). After 4 wk on these diets, ST was measured on all the mice. A second ST was recorded on each mouse by randomly sampling one-fourth of the population after 1, 2, 3, or 4 wk on a pelleted rodent food diet. Regardless of diet, R mice had shorter first and second ST than S mice (P < 0.01), suggesting higher hepatic Phase I microsomal enzyme activity. Mice on both phenobarbital-supplemented diets had shorter first ST than mice whose diets did not include that microsomal enzyme inducer (P < 0.01). In Exp. II, ST was measured on male and female R and S mice (n = 280) after they had been fed the E- diet for 2 wk, then the E+ diet for 2 wk, and then a pelleted rodent food diet for 2 wk. Growth response to the E+ diet was the percentage of reduction in gain on the E+ diet compared to gain on the E- diet the previous 2 wk. As in Exp. I, S mice slept longer than R mice (P < 0.01). The residual correlation between ST and gain reduction associated with the E+ diet equaled 0.04. Thus, an animal's apparent Phase I enzyme activity did not predict its growth rate depression on the toxin-containing diet. Based on these and previous studies, divergent selection for toxicosis response in mice was successful partially by causing divergence in activities of hepatic Phase I and II detoxification enzymes.


Subject(s)
Adjuvants, Anesthesia/pharmacokinetics , Mice, Inbred ICR/physiology , Pentobarbital/pharmacokinetics , Plant Poisoning/veterinary , Poaceae/microbiology , Selection, Genetic , Acremonium , Animal Feed/adverse effects , Animals , Female , Food Contamination , Genetic Predisposition to Disease , Liver/enzymology , Male , Mice , Mice, Inbred ICR/genetics , Plant Poisoning/genetics , Plant Poisoning/immunology , Time Factors
11.
Brain Res Brain Res Protoc ; 10(1): 47-54, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12379437

ABSTRACT

Toluene and many toluene-containing products are abused via inhalation. Previous investigations have used the place preference paradigm to evaluate the rewarding effects of commonly abused drugs such as morphine, cocaine, and amphetamine. A conditioning paradigm of toluene inhalation was developed in order to estimate the rewarding effect in mice. Conditioning sessions (five for toluene, five for air) were conducted twice daily for 5 days using a newly developed airtight inhalation shuttlebox (15x30x15 cm: wxlxh), which was divided into two compartments of equal size. One compartment was white with a textured floor, and the other was black with a smooth floor. All conditioning sessions were 20 min in duration, with a minimum of 7 h between sessions. Test sessions were carried out 1 day after the final training session with mice in a drug-free state. The time spent in each compartment during a 20-min session was measured using a digital video camera. Exposure to toluene vapors (700-3200 ppm) produced a significant conditioned place preference in mice. These results suggest that the conditioned place preference procedure using the newly developed airtight inhalation shuttlebox constitutes an important tool for studying the rewarding effect of abused solvents.


Subject(s)
Conditioning, Psychological/drug effects , Drug Delivery Systems/methods , Mice, Inbred ICR/physiology , Neuropsychological Tests/standards , Reward , Substance-Related Disorders/physiopathology , Toluene/pharmacology , Administration, Inhalation , Animals , Atmosphere Exposure Chambers , Behavior, Animal/drug effects , Behavior, Animal/physiology , Body Weight/drug effects , Body Weight/physiology , Brain/drug effects , Brain/metabolism , Conditioning, Psychological/physiology , Dose-Response Relationship, Drug , Drug Delivery Systems/instrumentation , Drug Tolerance/physiology , Environment, Controlled , Housing, Animal/standards , Hyperkinesis/chemically induced , Hyperkinesis/physiopathology , Male , Mice , Mice, Inbred ICR/psychology
12.
Exp Anim ; 51(2): 119-24, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12012718

ABSTRACT

To evaluate the phenotypic variation within a commercial outbred mouse stock, we examined sleep-time (or duration of loss of righting reflex) of outbred ICR mice after i.p. injection of ethanol (4.0 g/kg of body weight), urethane (1.3 g), tribromoethanol (250 mg), and pentobarbital (60 mg), and after i.v. injection of propofol (30 mg). We observed high-grade individual differences in sleep-time that ranged from 0 to 179 min, 83.1 +/- 4.3 (mean and SEM of 100 mice) for ethanol; 0 to 169 min, 64.5 +/- 3.1 for pentobarbital; 0 to 160 min, 36.6 +/- 3.6 for urethane; 0 to 120 min, 21.5 +/- 2.2 for tribromoethanol; and 3 to 20.5 min, 7.1 +/- 0.3 for propofol. This extensive phenotypic variance within the outbred stock was as great as the variation reported among inbred strains or selected lines, and the varied susceptibility within the colony was inherited by Jcl:ICR-derived inbred strains IAI, ICT, IPI, and IQI. The range of sleep-time variance for ethanol, pentobarbital, urethane, tribromoethanol, and propofol within four-way cross hybrid Jcl:MCH(ICR) mice was 86.6%, 63.3%, 124%, 61.0%, and 53.1% that of outbred Jcl:ICR mice, respectively. The present study indicates that phenotypic variance within an outbred Jcl:ICR stock was at high risk for susceptibility to the drugs that depress the central nervous system and that Jcl:ICR-derived inbreds may be an excellent source of animal models for studying the anesthesia gene.


Subject(s)
Ethanol/analogs & derivatives , Ethanol/pharmacology , Hypnotics and Sedatives/pharmacology , Mice, Inbred ICR/genetics , Sleep/drug effects , Animals , Crosses, Genetic , Female , Genetic Variation , Male , Mice , Mice, Inbred ICR/physiology , Pentobarbital/pharmacology , Phenotype , Propofol/pharmacology , Sleep/genetics , Sleep/physiology , Species Specificity , Time Factors , Urethane/pharmacology
13.
Article in English | MEDLINE | ID: mdl-10582317

ABSTRACT

Comparisons of metabolic properties of mitochondria from an endothermic and an ectothermic vertebrate were performed. Oxygen (O2) consumption rates of liver mitochondria from laboratory mice and western fence lizard (Sceloporus occidentalis) were determined over a range of temperatures (10, 20, 30 and 37 degrees C) and in the presence of a variety of substrates. At 37 degrees C the O2 consumption rate of mouse mitochondria was 4-11 times higher than lizard mitochondria in the presence of five of eight substrates. This range of differences is similar to differences reported for O2 consumption of endothermic animals, tissues and cells over those of ectotherms. Thermal sensitivity of mitochondria was measured by calculation of Q10s for O2 consumption. Q10s were highest for mouse mitochondria overall. The range that showed the highest Q10s for the mouse mitochondria was 30-20 degrees C, whereas for the lizard mitochondria it was 20-10 degrees C. Thus, mitochondria from the ectotherm showed a lower degree of temperature sensitivity than did mitochondria from the endotherm. The preferred substrate for all mitochondria at all temperatures was succinate, but mouse mitochondria then showed some preference for alpha-ketoglutarate and citrate, whereas lizard mitochondria showed a preference for pyruvate and malate + pyruvate.


Subject(s)
Body Temperature Regulation/physiology , Mitochondria/metabolism , Oxygen Consumption/physiology , Animals , Citrates/pharmacology , Lizards/physiology , Mice , Mice, Inbred ICR/physiology , Mitochondria, Liver/metabolism , Oxygen Consumption/drug effects , Succinates/pharmacology , Temperature
14.
J Comp Neurol ; 398(1): 139-50, 1998 Aug 17.
Article in English | MEDLINE | ID: mdl-9703032

ABSTRACT

Neurturin (NTN) and glial cell line-derived neurotrophic factor (GDNF) are the first two members of the GDNF family (GF) of neurotrophic factors. These two proteins are potent survival factors for several populations of central and peripheral neurons in mature and developing rodents. The receptor for these factors is a multicomponent complex that includes the RET (rearranged during transfection) tyrosine kinase receptor and one of two glycosyl phosphatidylinositol (GPI)-linked ligand-binding components called GDNF family receptor alphas (GFRalpha-1 and GFRalpha-2). We have used in situ hybridization to study the mRNA expression of NTN, GDNF, RET, GFRalpha-1, and GFRalpha-2 in the central nervous system (CNS) of adult mice. GF receptors are expressed in several areas in which neuronal populations known to respond to NTN and GDNF are located, including the ventral horn of the spinal cord and the compacta region of the substantia nigra. In addition, we have demonstrated receptor expression in other areas of the brain including the thalamus and hypothalamus. Neurons in these areas express GF receptors, and therefore, may respond to NTN or GDNF. NTN and GDNF are expressed in targets of neurons that express GF receptors. The pattern of GF factor and receptor expression in the adult brain suggests a role for these factors in maintaining neuronal circuits in the mature CNS.


Subject(s)
Drosophila Proteins , Mice, Inbred ICR/physiology , Nerve Growth Factors/genetics , Nerve Tissue Proteins/genetics , Neuroprotective Agents/metabolism , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Age Factors , Animals , Brain Chemistry/physiology , Brain Stem/chemistry , Brain Stem/cytology , Cerebellum/chemistry , Cerebellum/cytology , Female , Gene Expression/physiology , Glial Cell Line-Derived Neurotrophic Factor , Glial Cell Line-Derived Neurotrophic Factor Receptors , Hypothalamus/chemistry , Hypothalamus/cytology , In Situ Hybridization , Mesencephalon/chemistry , Mesencephalon/cytology , Mice , Neurturin , Olfactory Bulb/chemistry , Olfactory Bulb/cytology , Prosencephalon/chemistry , Prosencephalon/cytology , Proto-Oncogene Proteins c-ret , RNA, Messenger/analysis , Spinal Cord/chemistry , Spinal Cord/cytology , Thalamus/chemistry , Thalamus/cytology
15.
Theriogenology ; 49(7): 1397-407, 1998 May.
Article in English | MEDLINE | ID: mdl-10732076

ABSTRACT

This study was conducted to determine whether inbreeding coefficients of selected parents or of progeny differed between lines of mice selected for increased or decreased responsiveness to a nutritional toxicosis. A second objective was to determine whether the influence of inbreeding of parents and/or progeny on reproductive traits differed between those lines. Mice were selected divergently for 8 generations for the effect on post-weaning growth of endophyte-infected fescue seed in their diet. Forty pairs (or in Generation 7, 20 pairs) were selected and mated per generation in each line. Inbreeding increased 0.5 to 0.6% per generation in both lines, a rate close to that predicted from genetic theory. Inbreeding coefficients of selected parents were not higher in the susceptible than in the resistant line. A difference would have been expected if the inbreeding coefficient had been correlated with susceptibility to toxicosis. The magnitudes of inbreeding depression for reproductive traits did not differ significantly between lines. The average inbreeding coefficient of the potential litter tended to be higher in nonfertile than fertile matings (P = 0.10), but inbreeding coefficients of sires and dams did not differ between successful and unsuccessful matings. Inbred litters tended to be born earlier than noninbred litters (P = 0.10). Inbred dams produced smaller litters than noninbred dams (main effect P < 0.05) but only when the litter also was inbred (interaction P < 0.01). Sex ratio was not influenced by inbreeding of sire, dam or litter, but there was a higher proportion of male progeny in the susceptible than in the resistant line (P = 0.01). To avoid reduced reproductive fitness, laboratory animal populations should be managed to minimize inbreeding of progeny and dam.


Subject(s)
Inbreeding , Mice, Inbred ICR/genetics , Plant Poisoning/veterinary , Poaceae/poisoning , Animals , Female , Litter Size , Male , Mice , Mice, Inbred ICR/physiology , Plant Poisoning/genetics , Pregnancy , Pregnancy Rate , Random Allocation , Sex Ratio , Toxins, Biological/poisoning , Weight Gain
16.
J Anim Sci ; 75(8): 2165-73, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9263065

ABSTRACT

In three experiments, mice from lines selected for resistance (R) or susceptibility (S) to growth depression from endophyte-infected fescue seed in the diet were fed diets containing infected (E+) or non-infected (E-) seed. Activities of liver enzymes known to participate in oxidation, reduction, or hydrolysis or in conjugation of xenobiotics were measured in these mice. In all experiments, E+ caused greater reduction in initial ADG of S than of R mice. In Exp. 1, liver cytochromes P450 and b5 activities were not affected by line, diet, or their interaction. These enzymes were not evaluated in subsequent experiments. In all experiments, glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (GRT) activities differed between lines. Resistant mice had significantly higher GST activity on both diets in Exp. 1, on E- in Exp. 2, and on E+ in Exp. 3. Resistant mice had higher GRT activities on E+ in Exp. 1, on E- in Exp. 2, but after 4 wk on either diet in Exp. 3. Before test diets were imposed in Exp. 3, GST and GRT activities were higher in R-line mice. Divergent selection created lines that differed in response to tall fescue in the diet. Postweaning growth of resistant mice was less severely depressed by E+, although susceptible mice later expressed compensatory gain. Activities of two detoxification enzymes generally were higher in livers from R-line mice, suggesting a biochemical mechanism for the difference. Using such traits, it may be possible to select ruminants for resistance to fescue toxicosis.


Subject(s)
Genetic Predisposition to Disease , Mice, Inbred ICR/genetics , Mice, Inbred ICR/physiology , Plant Poisoning/veterinary , Poaceae/microbiology , Selection, Genetic , Animals , Breeding , Female , Glutathione Transferase/analysis , Growth/genetics , Growth/physiology , Hydrolysis , Liver/enzymology , Male , Mice , Mice, Inbred ICR/growth & development , Models, Biological , Oxidation-Reduction , Plant Poisoning/physiopathology , Plant Poisoning/prevention & control , Weight Gain/physiology
17.
J Nutr ; 126(11): 2851-60, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8914957

ABSTRACT

Five-wk-old male mice from high growth (M16) and randomly bred control (ICR) lines, plus their reciprocal crosses, ICR x M16 and M16 x ICR, were used to investigate whether whole-body O2 consumption, jejunal respiration, jejunal glucose absorption and the apparent energetic efficiency of jejunal active glucose uptake in mice are altered by genetic selection for growth as well as by heterosis and maternal effects. Whole-body O2 consumption was measured in 12 mice from each line or cross. The mice were later killed for measurement of jejunal O2, using tissue respiration chambers and jejunal glucose transport determined by 3H-3-O-methylglucose accumulation. No heterosis or maternal effects were detected in jejunal glucose active transport and active glucose uptake. Selection for growth (M16 vs. ICR) increased daily gain (1.54 vs. 1.09 g, P < 0.001), small intestinal length and weight, but did not enhance jejunal glucose transport. The apparent energetic efficiency of jejunal active glucose uptake among lines was not different (54.0, 50.4, 51.6 and 47.1 nmol ATP expended/nmol glucose uptake for M16, ICR, M16 x ICR and ICR x M16, respectively, P > 0.63). Selection for growth in mice did not result in more energetically efficient jejunal glucose absorption.


Subject(s)
Energy Metabolism/physiology , Glucose/pharmacokinetics , Jejunum/metabolism , Mice, Inbred ICR/growth & development , Mice, Inbred ICR/physiology , Selection, Genetic , Animals , Breeding , Hybrid Vigor/physiology , Male , Mice , Mice, Inbred ICR/genetics , Oxygen Consumption/physiology
18.
Chronobiol Int ; 10(5): 338-48, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8261533

ABSTRACT

The effects of the time of day of drug administration on the subchronic toxicity and pharmacokinetics of gentamicin, as well as the role of feeding schedule on circadian rhythms, were investigated in mice. ICR male mice were housed in a light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase) for 1 day or 14 days before drug administration. The animals were given a single subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for 18 days for the subchronic toxicity studies. A significant dosing-time dependency was shown for mortality and body weight loss, with higher values at midlight and lower ones at the middark (p < 0.05). A significant circadian rhythm was also found for gentamicin kinetics in ALF mice, with the highest clearance at middark and the lowest one at midlight (p < 0.01). The kinetic rhythm of gentamicin coincided well with the toxicity rhythm of the drug. The TRF schedule had a marked influence on the rhythms of gentamicin kinetics and toxicity, showing lowest clearance and higher toxicity at middark. The rhythm of subchronic toxicity of gentamicin seems to be due, at least in part, to the rhythm in kinetics and is strongly influenced by the feeding schedule. Thus, the timing of dosing is an important factor in the kinetics and the subchronic toxicity of gentamicin administration in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.


Subject(s)
Circadian Rhythm , Eating/physiology , Gentamicins/pharmacokinetics , Gentamicins/toxicity , Mice, Inbred ICR/physiology , Animals , Feeding Behavior , Male , Mice , Time Factors , Weight Loss/drug effects
19.
Toxicol Lett ; 66(1): 47-52, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8427020

ABSTRACT

It is well known that the oral administration of di-2-ethylhexyl phthalate (DEHP) produces severe seminiferous tubular atrophy in rats, but mice are far less sensitive. In the present experiment, we demonstrated that one strain of mice derived from ICR mice, Crj:CD-1, was very sensitive to DEHP-induced testicular injury. This atrophy was accompanied by lowered zinc concentration and lactate dehydrogenase isozyme X in the testis. This fact and the effect of genetic background will need to be considered for assessing the risk of testicular toxicity in men exposed to phthalate esters.


Subject(s)
Diethylhexyl Phthalate/toxicity , Mice, Inbred ICR/physiology , Testis/pathology , Animals , Atrophy/chemically induced , Body Weight/drug effects , Isoenzymes , L-Lactate Dehydrogenase/metabolism , Liver/anatomy & histology , Liver/drug effects , Male , Mice , Organ Size/drug effects , Sensitivity and Specificity , Species Specificity , Testis/anatomy & histology , Testis/drug effects , Zinc/metabolism
20.
J Anim Sci ; 69(2): 543-50, 1991 Feb.
Article in English | MEDLINE | ID: mdl-2016184

ABSTRACT

Performance of six genetic groups of mice was studied in three different environments in order to determine the effect of heterosis on consistency of performance in varied environments. Designed as a 3 x 6 factorial, data were analyzed using least squares analyses of variance. Genetic group effects, environmental effects, genetic group x environment interaction, and heterosis were examined for 42-d weight, age and weight at vaginal opening, age and weight at puberty, ovulation rate (determined by total corpora lutea), number of implantations, and number of fetuses at 10 d of gestation. Weight at vaginal opening, ovulation rate, implantation rate and total number of fetuses exhibited significant heterosis. Regression of these traits against an environmental index (mean performance of all genetic groups over environments) provided an estimate of stability of performance. In general, genetic groups exhibiting heterosis expressed more consistent performance across environments than pure lines did. We conclude that a stability model could be used to aid in identification of lines with consistent performance for production traits in variable environments.


Subject(s)
Breeding , Heterozygote , Homeostasis , Hybrid Vigor/physiology , Mice/genetics , Analysis of Variance , Animals , Embryo Implantation/genetics , Female , Litter Size/genetics , Male , Mice/physiology , Mice, Inbred ICR/genetics , Mice, Inbred ICR/physiology , Ovulation/genetics , Regression Analysis , Sexual Maturation/genetics , Temperature
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