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Murine models of polycystic kidney disease.

The current knowledge of human polycystic kidney disease (PKD)--its morphology as well as the current biochemical and molecular understanding of the disease- has been enormously aided by the existence of a variety of animal models. In mice, several spontaneous mutations have been identified that give rise to PKD. Furthermore, it has been possible to create experimental models of renal cystic disease by genetic manipulation. All these different models have been very informative in studying the role of growth hormones, cell differentiation and hyperplasia, ionic transport, oncogene expression and changes in extracellular matrix (ECM) composition during the development of PKD. Furthermore, they have allowed investigators to test different therapeutic approaches in vivo. This article will review the characteristics of the most common murine models of PKD, some of their current uses and the future role of these animal models in the understanding of human renal cystic disease.

Animals↗

Numerical analysis of electrophoretic protein patterns of Streptobacillus moniliformis strains from human, murine and avian infections.

A total of 31 cultures representing 22 different strains of Streptobacillus moniliformis has been characterised by unidimensional SDS-PAGE of cell proteins. The isolates were from sporadic and outbreak cases of human infection in the USA, UK and France, as well as mouse, turkey and rat isolates from various countries. The protein patterns, which contained 40-50 discrete bands, were highly reproducible and were used as the basis for a numerical analysis. Three clusters were obtained at the 86% similarity (S) level and these were further divided to give a total of seven clusters at the 90% S level. S. moniliformis strains, irrespective of the original host or geographical location of isolation, had a characteristic protein profile that enabled them to be easily distinguished from allied unclassifiable organisms. The analysis showed that Haverhill fever strains can be clearly distinguished from rat-bite fever strains. Protein-band differences amongst the latter strains corresponded with different geographical locations. We conclude that high resolution PAGE combined with computerised analysis of protein profiles provides the basis for typing clinical isolates of S. moniliformis. Seven PAGE types were identified and reference strains for each have been designated as a basis for future studies.

Animals↗

Acquired immunity to larvae of Amblyomma marmoreum and A.hebraeum by tortoises, guinea-pigs and guinea-fowl.

A study of acquired resistance in guinea-pigs, guinea-fowl and tortoises to larvae of the ticks Amblyomma hebraeum Koch and A.marmoreum Koch (Acari: Ixodidae) showed that repeated infestations of the laboratory host resulted in a 29.3-49.4% reduction respectively in weight of engorged larvae. No resistance was induced in guinea-fowl, the natural host for larvae of both species. A small decline in the mean weight of engorged larvae was observed for both species of ticks after three successive infestations on tortoises. The reduction in weight was more pronounced in A.hebraeum (14.5%) which does not naturally feed on tortoises than for A.marmoreum (8.4%), a common tick on this host. The occurrence of acquired resistance in natural tick host relationships as opposed to unnatural tick host relationships is discussed.

Animals↗

Animal models for nervous system disease in systemic lupus erythematosus.

Animal models have much to teach us about nervous system dysfunction in SLE. It should be stressed that the murine strains described in this review have variable expression in the onset and severity of clinical and serological features, perhaps making them more like a heterogeneous human population with SLE. With this in mind, studies involving animal models like those involving human subjects should use a sample size that ensures adequate power. It is not surprising that studies that use sample sizes as low as four to five animals per group would find discrepant results, especially in outcomes that are measured prior to the terminal phases of the disease. Similar to human SLE patients, murine models have systemic autoimmune as well as neurological manifestations. Studies with murine models must continue to consider some type of SLE disease activity measures in order to control for the effects of systemic disease on nervous system dysfunction. Because of the short time window between the earliest evidence of neurologic dysfunction and severe autoimmune disease manifestations, especially in MRL/lpr mice, the disease acceleration model may allow a more careful dissection of how immunological events are related to nervous system dysfunction. Alternatively, the study of MRL/lpr mice ultraearly (e.g., 3 weeks of age) could also provide invaluable information about the first events leading to nervous system dysfunction in SLE. Both approaches promise to identify predictors of specific nervous system manifestations that may suggest novel and more specific therapeutic interventions.

Animals↗

Comparison of Chalquest and Hayflick media, with and without ammonium reineckate, for isolating Mycoplasma pulmonis from rats.

Chalquest and Hayflick media with and without ammonium reineckate were compared for isolation of Mycoplasma pulmonis from the nasopharyngeal ducts, tracheobronchial trees, and middle ears of 66 naturally infected rats. The results show that 92% (366 of 396) of the samples were positive for M. pulmonis in Chalquest medium with and without ammonium reineckate and 66% (260 of 396) were positive in Hayflick medium with and without ammonium reineckate (P less than 0.001). An enhancing effect of ammonium reineckate on M. pulmonis isolation was observed only in Hayflick medium; the isolation rate was 76% (151 of 198) in Hayflick medium with ammonium reineckate as compared with 55% (109 of 198) in Hayflick medium without ammonium reineckate (P less than 0.03). No significant differences in isolation rates were observed between Chalquest medium with and without ammonium reineckate. The mean growth time of M. pulmonis on Chalquest medium was 3.4 days as compared with 5.1 days in Hayflick medium, indicating that M. pulmonis can be detected earlier on Chalquest medium than on Hayflick medium. These data indicate that Chalquest medium is superior to Hayflick medium for M. pulmonis isolation from rats.

Animals↗

Postmortem findings in captive cane rats (Thryonomys swinderianus) in Gabon.

The causes of morbidity and mortality in a population of cane rats (Thryonomys swinderianus) on an experimental farm in Gabon were monitored for 21 months; 94 of 546 animals (17.2 per cent) died and were examined postmortem, and complementary laboratory examinations were carried out on 23 of the cases together with samples from 13 other animals kept elsewhere in similar conditions. Twenty-six (28 per cent) of the deaths occurred in preweaned kits, 40 (42 per cent) in subadults and 28 (30 per cent) in adults. The average monthly mortality was 2.5 per cent. Trauma was responsible for 29 of the deaths, 12 were due to septicaemia, 10 to primary respiratory lesions, five to digestive disorders, four to urinary lesions, three to reproductive problems and three to other causes; no diagnosis could be reached in 28 cases.

Animals↗

A model for adhesion formation by thermal injury in the abdominal cavity of the mouse.

An experimental model for inducing peritoneal adhesions in mice is described. Measurable thermal trauma can be inflicted by the application of a heated metal object, for a given lapse of time, to the surface of a section of mouse intestine. Parameters of temperature, area and application time were so manipulated as to obtain adhesions in only 70-75% of treated mice. It is maintained that this model can enable better evaluation of various prophylactic means and also the detection of exacerbating agents.

Animals↗

Hemorrhagic necrosis of the central nervous system. A spontaneous disease of fetal hamsters.

During studies of transplacental virus infections in random bred hamsters purchased with timed pregnancies from three commercial dealers, spontaneous hemorrhagic necrosis of the central nervous system was seen in fetuses harvested near term. Ninety-seven pregnant hamsters from three colonies were examined during a 6-month period; this condition was seen in 25 of 41, 19 of 36, and five of 20 litters. Hamsters from another commercial colony were received, housed, and fed under the same conditions, but remained free of the disease. The pathological process was characterized by multiple spreading zones of edema, malacia, and hemorrhage. Lesions were restricted to neural tissues, including the retina and internal ear. Neuroepithelial proliferation with rosette formation, accompanying the destructive process, constituted a striking reparative response. No inflammatory reaction or cytopathic effects suggestive of virus-induced disease were seen. Studies on the cause of this condition were negative at the time when the disease disappeared spontaneously.

Animals↗

Effects of an individually ventilated cage system on the airway integrity of rats (Rattus norvegicus) in a laboratory in Brazil.

The ventilation method used in the management of laboratory rats is important in maintaining their health. Rats kept under general diluting ventilation (GDV) are exposed to high levels of pollutants present in the environment (dust, airborne bacteria, etc.) or those pollutants produced by animal metabolism and excretion inside the boxes (e.g. ammonia and carbon dioxide). These pollutants may contribute to respiratory pathologies. An alternative experimental ventilation system for laboratory animal housing using intracage ventilation technology (individually ventilated cage system, IVC) was developed. In this system, ammonia levels decreased and rats exhibited better reproductive performance and a lower incidence of pneumonia than rats maintained under GDV. Using two different levels of air speed (0.03-0.26 m/s: IVC(1); 0.27-0.80 m/s: IVC(2)), the effects of IVC were compared with GDV (control) in Wistar rats in terms of respiratory mucus properties, on the nasal epithelium (as measured by quantitative morphometry) and on the lungs (as determined by the cellular composition obtained by bronchoalveolar lavage). Mucus of the respiratory system was evaluated using the following techniques: rheology (viscoelasticity) by microrheometer, in vitro mucociliary transportability (frog palate) and contact angle (an indicator of adhesivity). Also, membrane transepithelial potential difference was measured as a biomarker of airway integrity. After bedding was changed, ammonia concentrations inside the cages on day 3 were significantly higher for GDV than for IVC(1) and IVC(2). The potential-difference values for IVC(1), IVC(2) and GDV in the epiglottis and in the trachea also showed differences. Although some significant differences were observed across the three groups in counts of some cell types, the intragroup results were highly variable among individuals and inconsistent between sexes. No significant differences in the other parameters were found across groups. These results establish that rats maintained under GDV in relatively unregulated conditions are exposed to factors that can lead to deleterious effects on the ciliated epithelium of the airways, and that these effects can be prevented by the use of IVC.

Air Pressure↗