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Biomedical subjects

K Gärtner

Publications and source records attributed to K Gärtner.

At least 19 recordsLinked to original sources

Effects of cage enrichment on territorial aggression and stress physiology in male laboratory mice.

The activation of different neuroendocrine subsystems depends on the individual perception and coping with the challenging situation, the formulation of these relations by J.P. Henry represents a most useful concept also for the assessment of welfare consequences of particular caging variables. We investigated effects of cage enrichment on behaviour and neuroendocrine activations of male laboratory mice. Mice in enriched cages behaved more aggressive, lacked stable dominance hierarchies and exhibited neuroendocrine alterations depending on their individual social position. Subdominant passive mice were characterized by an augmented adrenal capacity to synthesize epinephrine despite low activities of the tyrosine hydroxylase. Dominant mice showed elevated circulating corticosterone concentrations despite high tyrosine hydroxylase-activities. Findings showed a dissociation of neurosympathetic and adrenomedullary components in subdominant passive mice and a simultaneous activation of sympathetic adrenomedullary and hypothalamo-adrenocortical components in dominant mice. Within the conceptual framework of the Henry model this would suggest different deteriorations of welfare in dominant and subdominant passive mice. In the situation of intensified aggression in the enriched cages the increased epinephrine synthesis in subdominant mice reflect their more frequent receipt of attacks and the elevated corticosterone secretion in dominant mice reflect their hindered ability to control the dominant position.

Adaptation, Psychological↗

Changes in pulmonary calcitonin gene-related peptide and protein gene product 9.5 innervation in rats infected with Mycoplasma pulmonis.

Changes in the expression of calcitonin gene-related peptide (CGRP) and polyneural protein gene product 9.5 (PGP) in hilar peribronchial innervation was investigated by immunohistochemistry in specific pathogen-free rats chronically infected with Mycoplasma pulmonis. Image analysis of immunostained sections revealed a reduction of approximately 62% in the amount of CGRP- and PGP-immunoreactive innervation of the peribronchial area in the infected animals. The portion of the total bronchial perimeter occupied by bronchus-associated lymphoid tissue was increased six-fold. The decrease in the CGRP-immunoreactive area could be the result either of an enhanced CGRP release or of a loss of nerve fibres. The decrease in the PGP-immunoreactive fibres indicates a degenerative loss of nerves. Increased bronchus-associated lymphoid tissue and decreased bronchial innervation by neurons releasing the immunomodulatory neuropeptide CGRP might both contribute to the pathophysiology and symptoms of mycoplasmosis in the rat.

Animals↗

Dissociation between adrenal tyrosinehydroxylase and phenylethanolamine N-methyltransferase activities following repeated experience of defeats in individually housed male DBA/2J mice.

Adrenal activities of tyrosinehydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were compared between individually housed defeated intruders and socially housed residents (SR) (Experiment 1), and between individually housed defeated intruders and individually housed victor residents (Experiment 2). In addition, corticosterone titers were determined and dominance status of SR (dominant, subdominant active, and subdominant passive) considered. Defeats were induced twice a week for 6 consecutive weeks in short resident-intruder encounters. The main findings were: 1) within the groups of SR, TH and PNMT activities were high in dominant and low in subdominant-passive mice; 2) in Experiment 1, TH activities of individually housed defeated intruders were low like those of subdominant-passive SR whereas their PNMT activities were high like those of dominant SR; 3) in Experiment 2, TH activities were low in both categories of individually kept mice whereas PNMT activities were significantly elevated in the defeated intruders; 4) in both experiments, PNMT activities of intruders correlated significantly with the accumulated number of attacks they had received throughout all resident-intruder tests. Findings show separate effects of permanent social stimulation and of episodic experience of defeats on adrenal catecholamine synthesis. Lack of permanent social stimulation decreased adrenal TH and PNMT activities whereas repeated episodic experience of defeats specifically increased PNMT but not TH activities in individually housed mice.

Adrenal Glands↗

Response of rat colonic mucosa to a high fiber diet.

Secreting lubricating mucins, colonic crypt goblet cells, contribute to the intestinal protection against mechanical challenge. After feeding germ-free (GF) and specific pathogen-free (SPF) AS/Ztm rats for 6 weeks, the proliferative response of colonic goblet to a commercial bulky diet (37.1% fiber) was compared to that of a standard diet. (4.4% fiber). An increased uptake of the high fiber diet by GF rats significantly augmented the capacity for mucin secretion as indicated by the amount and length of crypts, crypt cells and mature goblet cells. The response of SPF rats was limited to a crypt elongation, generated by more crypt cells. In both study groups, the goblet cell replication activity was similar to their controls. The increase in the mucin-secreting capacity, induced by a constant mechanical challenge, highly suggests an improved intestinal protection.

Animals↗

[Dorsal recumbency in dogs--a circulatory risk during surgical treatment?].

In this study, changes in hemodynamic, blood gas, and metabolic variables recorded during right lateral and dorsal recumbency in beagles anaesthetised with thiopental are presented. Other than reported in human beings, dorsal recumbency in these dogs resulted in an increase (33%) in heart rate, decrease (30%) in systolic, diastolic, and mean systemic arterial pressure, a decrease (17%) in systemic vascular resistance, and a decrease in both right (31%) and left (39%) ventricular work in comparison with lateral recumbency. Furthermore, mixed-venous PO2, oxygen saturation and respiratory quotient were lower in dorsal than in lateral recumbency while O2 consumption and lipolysis were increased in the former. The changes presented may have been caused by beta-adrenergic stimulation in dorsal recumbency. It needs to be studied if capillary perfusion can be maintained adequately during surgery in dorsal recumbency or if this predisposes to cardiovascular shock.

Anesthetics, Intravenous↗

Effects of environmental enrichment on aggressive behavior, dominance hierarchies, and endocrine states in male DBA/2J mice.

Adult male mice (DBA/2J) siblings were housed three per cage for 6 wk, either in standard cages (SC) or in enriched cages (EC). Both attacks among group members and attacks against strange intruders were monitored once a week within each of 22 experimental groups. According to its attacking behavior, each mouse was categorized into one of three dominance categories: dominant, subdominant active, subdominant passive. Aggressive behavior and social organization were compared between the two types of housing conditions, and the effects of housing condition and dominance category on endocrinological and some organometrical parameters were analysed. The main findings were: (a) Mice in EC attacked intruders significantly more frequently compared to mice in SC; (b) In EC groups the position of the dominant male was less stable than in SC groups; (c) Plasma corticosterone titers (PCT) were significantly elevated in EC. Activities of tyrosinehydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) did not differ significantly between the housing conditions; (d) TH and PNMT activity were significantly enhanced in the dominant males of SC groups compared to subdominant passive males. Intermediate activities for both enzymes were determined for subdominant active males; and (e) PCT were significantly elevated in dominant males of the EC groups compared to subdominant active and subdominant passive males and also compared to the dominant males in the SC groups. Findings suggest that keeping adult male mice in structured cages can result in increased aggression towards intruders, a change in the social organization, and altered endocrine states, depending on the individual dominance position.

Aggression↗

The cage design affects intermale aggression in small groups of male laboratory mice: strain specific consequences on social organization, and endocrine activations in two inbred strains (DBA/2J and CBA/J).

Effects of the enrichment of conventional laboratory housing cages with an additional labyrinth on intermale aggression, social organization, and activations of the pituitary-adrenocortical and sympathetic-adrenomedullary neuroendocrine subsystems are compared between adult male DBA/2J and CBA/J mice, differing genetically in their intermale aggression. Mice of both strains were kept three per cage for six weeks either in standard laboratory cages (SC) or in enriched cages (EC). Intermale aggression against a strange intruder and between cagemates was monitored once a week within each group. Dominance relations were derived from the distribution of attacks within a group. Plasma corticosterone titers (PCT) and activities of the tyrosinehydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were determined for each mouse at the end of the study. The main findings were: 1. Intermale aggression increased in both strains in groups kept in EC. 2. In the more aggressive DBA/2J the pattern of social organization shifted from groups with a single permanent dominant mouse in SC to groups with a frequently changing dominant mouse in EC. 3. In CBA interchanges of the dominant mouse was prevailing and did not differ between the two housing conditions. 4. In DBA/2J mice PCT were significantly elevated in EC. 5. In CBA/J mice activities of TH and PNMT were significantly elevated in EC. 6. Body weight gain was significantly delayed in mice kept in EC in both strains. Findings revealed strainspecific environmental effects on both social organization and endocrine states. The PCT increase obtained only in DBA/2J indicate that alterations of the social relations between cagemates are more likely to induce states of stress than an increase in intermale aggression alone.

Aggression↗

Mechanical challenge causes alterations of rat colonic mucosa and released mucins. Alterations of mucosa and mucins.

The effect of intraluminal challenge on rat colonic mucin producing cells and the amount and composition of released mucins was investigated. Germfree rats (GF) were maintained on a commercial high fiber (HF) diet (37% of undigestable fiber, Altromin 1640 p), in order to increase volume, dry weight and abrasive effect of the ingesta. GF control rats were fed a standard (ST) laboratory diet with 4.5% fiber (Altromin 1314 f). In the HF diet group, histological sections of the proximal and distal colon revealed a significantly increased number of mucin secreting goblet cells and an elevated goblet cell replication activity, as determined by 5'-bromo-deoxyuridine incorporation. The total amount of colonic mucins, isolated by gel filtration, was increased versus the control group. According to the results of ion exchange chromatography, carbohydrate and amino acid analysis, mucins from rats, given the HF diet, had an elevated content of acidic mucin constituents with alterations in the carbohydrate and amino acid composition. In a parallel study with specified pathogen free rats (SPF), the additional influence of the microflora on mucin secreting cells and isolated mucins was determined. An increased number of mucin secreting cells predominantly was observed in rats given the standard diet. Due to bacterial degradation, significantly less mucin was isolated from both dietary groups. The increase of acidic mucin constituents was less pronounced than in GF rat mucin, coinciding with losses of terminally linked monosaccharides. Alterations of the core protein, accompanying the presence of the microflora, were not detected.

Amino Acids↗

Social isolation modifies the response of mice to experimental Mengo virus infection.

To investigate the effects of social isolation on host resistance male mice were housed either individually (IH) or in groups of four or five (GH). All animals were infected with MengoM,L virus. Incubation time (INCUB), duration of illness (ILL), death rate (DR), histopathological changes, and serum corticosterone levels (CORT) were recorded. First, the effect of IH starting 4 days prior to infection was studied in 5 different inbred strains. Next, the effect of different IH length was examined, and the role of T-cells was investigated by comparing euthymic (+/+) and athymic (nu/nu) NMRI mice. Finally, the effects of the infection on CORT in IH and GH mice were compared in C57BL/6 mice. The major findings were: 1. IH significantly increased ILL in all but the DBA/2 strain, whereas DR was not affected except in C57BL/6. 2. Longer IH (starting 35 [DBA/2] or 10 [NMRI] days prior to virus inoculation) significantly shortened INCUB and prolonged ILL, but IH starting on the day of virus inoculation [DBA/2] significantly prolonged INCUB and shortened ILL. 3. NMRI nude mice exhibited an unaltered DR accompanied by a tremendously prolonged INCUB. 4. Investigations in C57BL/6 mice revealed a significant rise of CORT after infection. This increase was higher in IH compared to GH mice. It is suggested that IH attenuates T-cell mediated inflammatory processes and/or increases macrophage activation, which in turn results in a prolonged course of the disease.

Animals↗

[Physiologic hypothermia of newborn kittens up to 6 weeks old].

Kittens showed a physiological hypothermia until they were 6 weeks of age. In the first 3 weeks of age rectal temperature was constantly low (37.6 +/- 0.3 degrees C). A linear increase of rectal temperature followed from the fourth to the sixth week of age inclusively and from the seventh week on rectal temperature reached the final temperature level (38.4 +/- 0.3 degrees C). This finding has to be considered in clinical assessment of kittens' body temperature.

Animals↗

The influence of genotypes and social ranks in the clinical course of an experimental infection with Mycoplasma pulmonis (MRM) in inbred rats.

Social ranks of healthy, adult male inbred rats housed in groups of four per cage were determined by their relative differences in intromission and ejaculatory patterns observed repeatedly under competitive copulatory conditions. Once ranked they were inoculated with M. pulmonis by contact with castrated females suffering clinically from M.pulmonis.--Body weight reduction and scores for laryngo-bronchotracheal breathing sounds and dispnoea or sneeze or wipe and the titers of specific antibodies were continuously observed during 123 days of illness. Studies were done in five series concerning the inbred strains AS/Ztm, LEW/Ztm, BH/Ztm. Genotypic differences accounts for 60-80% of the variability of the illness. LEW/Ztm was the most affected strain. Only in strain LEW/Ztm week correlations were shown between social rank before the infection (characterized by sexual activity under competitive conditions) and the scores for breathing sounds, dyspnoea and sneeze and wipe. Animals high in social rank showed a milder clinical course of the infection.

Animals↗

Changes in colonic mucins of germfree rats in response to the introduction of a "normal" rat microbial flora. Rat colonic mucin.

In order to determine the influence of bacterial colonization on amount and composition of colonic mucins, germfree male AS/Ztm rats were colonized with a rat specific intestinal flora for different times (2, 7, 14, 21, 28, 35, 120 days). The amount of colonic mucins was determined by gel filtration on Sepharose CL-4B; the relative amount of acidic mucins was calculated after ion exchange chromatography. In addition, cecal weight and dry matter of feces were monitored. While germfree and SPF rats revealed similar amounts of colonic mucins (7.0 vs. 7.2 mg mucin/300 g body weight), the initial phase of association was characterized by considerably decreasing values. After four weeks of association, the total amount of colonic mucins had almost equalized in the two groups. The amount of acidic mucins, having decreased during the first three weeks of colonization, rendered values comparable to the SPF mucins after four months of adaptation. Cecomegaly in germfree rats disappeared within the first two days, while solidification of the intestinal content occurred within four months. Mucin losses during initial phase of association are attributed 1. to the disappearance of the cecal mucin pool, and 2. to the mucin degrading activity of some bacterial strains known to be present in the intestinal flora. Further development is conducted by a stimulation of mucin secretion, described to follow the colonization. The initially increased secretion of neutral mucins is attributed to a pronounced release of immature mucin glycoproteins, while the shift to more acidic mucins is considered to result from stimulated secretion as well as from a selective bacterial degradation of neutral mucin components.

Animals↗

Life expectancy, its relation to sexual activity and body weight in male inbred mice.

Body weight of male mice of five inbred strains caged in groups of five was determined three times between the ages of 80 and 100 days, representing the individual fully grown body weight. Sexual activity of each mouse (number of ejaculations and intromissions) was estimated under competitive conditions between the ages of 120 and 150 days in eleven repetitions. Within all inbred strains only about half of the males displayed sexual activity when confronted with an estric female. The other do not. The animals remained in their cage groups until natural death after 727 +/- 215 days (C57BL/6), 638 +/- 260 days (BALB/c), 630 +/- 187 days (CBA), 560 +/- 230 days (DBA/2) and 317 +/- 62 (AKR) days. Only amongst the sexually active animals did individual life span correlate with the number of ejaculations. This was seen in C57BL/6, CBA and DBA/2. Particularly sexually successful animals, carrying out the most ejaculations, live 10-20% longer than their (subdominant) competitors displaying less sexual success. Sexually inactive males (characterised by no ejaculations and less other sexual activities) show that this characteristic of their personalities imposes no limitation upon their life expectancy. Fully grown body weight and the individual life span correlates within the strains DBA/2, C57BL/6 and BALB/c. Medium-sized animals have a greater life expectancy than small or large ones.

Animals↗

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo-infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin.

Animals↗

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 2. Athymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, in congenitally athymic rat strains. From 11 institutes around the world, we sampled 15 groups of animals at ages of 1 1/2-2 months and 1/2 year. The analysis included weight of body and spleen; antibody response and delayed-type hypersensitivity response after immunization with ovalbumin; and (immuno)histology of spleen, lymph nodes and lymphoid tissue along the gastrointestinal tract. Morphometric analysis was done for alpha beta-T-cell receptor-bearing cells in spleen tissue as a measure of the periarteriolar lymphocyte sheath; it was also done for splenic red pulp using the antibody ED2 recognizing red pulp macrophages. For almost all variables analyzed, statistically significant differences between the groups were observed. The extent of alpha beta-T-cell receptor-bearing cells in the spleen increased with age. The functioning of these cells in immunological responses can be questioned, because an immune response to ovalbumin was invariably absent. But secondary follicles with germinal centers, reflecting T-cell-dependent B-cell reactivity, were observed in lymph nodes and Peyer's patches (up to 40% and 75%, respectively, depending on the group), with a higher prevalence in older animals. A cluster analysis on the basis of body and spleen weight and composition of spleen compartments did not yield clusters with a different profile in regard to the animals' group of origin. The data presented are useful when comparing studies performed with various athymic rat strains at different institutes.

Animals↗

Strain differences in sensitivity of rats to Mycoplasma arthritidis ISR 1 infection are under multiple gene control.

At least 5 female rats from each of 24 inbred (ACI, AS, BDIX, BH, BN, BS, BUF, DA, LE, LEW, MWF, OM, SPRD-Cu3, W-Krypt, and WKY), RT1 congenic [BH.1L(LEW), LEW.1A(AVN), LEW.1C(WIST), LEW.1LV3(BH), LEW.1K(SHR), and LEW.1N(BN)], and F1 hybrid [(LEW x BN)F1, (LEW.1W x LEW.1A)F1, and (LEW x LEW.1W)F1] strains, representing eight independent major histocompatibility complex (MHC) haplotypes (a, b, c, dv1, k, l, n, and u) and five related RT1 haplotypes (av1, lv1, lv3, uv2, and uv3), were inoculated intravenously with Mycoplasma arthritidis, and the severity of the polyarthritis that developed was determined by estimating arthritis scores and weight reductions. The 24 inbred, congenic, and F1 hybrid rat strains differed considerably in their sensitivity to infection with M. arthritidis and in the severity of the polyarthritis that they developed. Statistical evaluation showed that in the acute phase (days 1 to 42 after infection) as well as in the chronic phase (days 39 to 121 after infection) of the disease, the means of the arthritis scores for the strains form a continuous variation without significant interruptions, with the very sensitive LEW rats, the RT1 congenic rats on LEW background, the F1 hybrids with LEW, and the MWF, BS, BH, and DA rats on one end and the resistant WKY, BUF, W-Krypt, LE, and OM rats on the other end. A continuous variation was also observed for the means of the growth rates. There were, however, no significant differences between the sensitive and the resistant rat strains in the antibody titers determined by complement fixation test and enzyme immunoassay. Heritabilities of arthritis scores were calculated for all strains (h2 = 0.39 to 0.62), for the RT1 congenic strains (h2 = 0.04 to 0.14), and for several strains with identical MHC genes (h2 = 0.61 to 0.93). The results show that non-MHC genes are probably responsible for the sensitivity of rats to infection with M. arthritidis.

Acute Disease↗

A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals?

This paper is a review of experiments, performed in our laboratory during the past 20 years, designed to analyse the significance of different components of random variability in quantitative traits in laboratory rats and mice. Reduction of genetic variability by using inbred strains and reduction of environmental variability by highly standardized husbandry in laboratory animals did not remarkably reduce the range of random variability in quantitative biological traits. Neither did a tremendous increase of the environmental variability (i.e., living in a natural setting) increase it. Therefore, the postnatal environment cannot be that important as the source of random variability. Utilizing methods established in twin research, only 20-30% of the range of the body weight in inbred mice were directly estimated to be of environmental origin. The remaining 70-80% were due to a third component creating biological random variability, in addition to the genetic and environmental influences. This third component is effective at or before fertilization and may originate from ooplasmic differences. It is the most important component of the phenotypic random variability, fixing its range and dominating the genetic and the environmental component. The Gaussian distribution of the body weights observed, even in inbred animals, seems to be an arrangement supporting natural selection rather than the consequence of heterogeneous environmental influences. In a group of inbred rats, the males with the highest chance of parenting the next generation were gathered in the central classes of the distribution of the body weight.

Animal Husbandry↗

Frequency distribution of body mass in groups of highly standardized laboratory rats are characterized by negative kurtosis.

8,600 laboratory rats (outbred and inbred, SPF) of 3 independent breeding and experimental units, divided into groups of in 80-100 animals of equal sex and age, were housed in groups of 5 animals of the same sex and age per cage under highly standardized (SPF) conditions. The body masses were determined monthly between 8 and 56 weeks of age. The frequency distributions of body mass per group (coefficient of variation 7-12%) very frequently showed small negative kurtosis (-0.12 to -0.76) but no general tendency to skewness. Kurtosis is small and seems to have been acquired before birth and had no genetic reasons because it was also present in groups of inbred strains and in animals not selected artificially after birth. It may be caused by shortages of both tails of the frequency distribution of the body mass.

Animals↗