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Hufeldt M.R.,Copenhagen University | Hufeldt M.R.,Center for Applied Laboratory Animal Research | Nielsen D.S.,Copenhagen University | Vogensen F.K.,Copenhagen University | And 2 more authors.
Comparative Medicine | Year: 2010

During recent years, the composition of the gut microbiota (GM) has received increasing attention as a factor in the development of experimental inflammatory disease in animal models. Because increased variation in the GM might lead to increased variation in disease parameters, determining and reducing GM variation between laboratory animals may provide more consistent models. Both genetic and environmental aspects influence the composition of the GM and may vary between laboratory animal breeding centers and within an individual breeding center. This study investigated the variation in cecal microbiota in 8-wk-old NMRI and C57BL/6 mice by using denaturing gradient gel electrophoresis to profile PCR-derived amplicons from bacterial 16S rRNA genes. Comparison of the cecal microbiotas revealed that the similarity index of the inbred C57BL/6Sca strain was 10% higher than that of the outbred Sca:NMRI stock. Comparing C57BL/6 mice from 2 vendors revealed significant differences in the microbial profile, whereas the profiles of C57BL/6Sca mice raised in separate rooms within the same breeding center were not significantly different. Furthermore, housing in individually ventilated cages did not lead to intercage variation. These results show that denaturing gradient gel electrophoresis is a simple tool that can be used to characterize the gut microbiota of mice. Including such characterizations in future quality-control programs may increase the reproducibility of mouse studies. Copyright 2010 by the American Association for Laboratory Animal Science.


Hufeldt M.R.,Copenhagen University | Hufeldt M.R.,Center for Applied Laboratory Animal Research | Nielsen D.S.,Copenhagen University | Vogensen F.K.,Copenhagen University | And 2 more authors.
Laboratory Animals | Year: 2010

The gut microbiota (GM) may influence disease expression in several animal models for inflammatory diseases. It may therefore seem reasonable to pursue reduction in the number of animals used for individual studies by reducing the variation in the GM. Previous studies have shown that the composition of the GM is related to genetics to a certain extent. We hypothesized that the GM similarity in a group of mice born by mothers not being sisters would be lower than that in a group born by mothers being sisters. The lower similarity could lead to clustering of the GM of mice born by non-sisters according to their mothers, while such clustering would not be visible if the mothers were sisters. We used 16S rRNA gene (V3 region) polymerase chain reaction-derived amplicon profiling by denaturing gradient gel electrophoresis (DGGE) to study the GM composition in caecum samples of 33 eight-week-old C57BL/6Sca mice from a breeding set-up with dam breeders that were sisters, as well as caecum samples of 35 eight-week-old C57BL/6Sca mice from a breeding set-up with dam breeders that were not sisters. Principal component analysis revealed a significant difference between the litters from the breeding set-up with dam breeders that were not sisters, whereas no significant difference between the litters based on the breeding set-up with dam breeders that were sisters was observed. The results obtained indicate that the systematic variation in the GM of inbred mice can be reduced by increasing the family relatedness of the breeding pairs.


Ellekilde M.,Copenhagen University | Krych L.,Copenhagen University | Hansen C.H.F.,Copenhagen University | Hufeldt M.R.,Copenhagen University | And 7 more authors.
Research in Veterinary Science | Year: 2014

Gut microbiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gut microbiota of a T2DM mouse model with a long term vision of being able to target the gut microbiota to reduce the number of animals used in experiments. Male B6.V-Lepob/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gut microbiota. All findings were thereafter correlated to one another in a linear regression model. The total gut microbiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gut microbiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gut microbiota may contribute to variation in various disease read-outs in the B6.V-Lepob/J model and considering them in both quality assurance and data evaluation for the B6.V-Lepob/J model may have a reducing impact on the inter-individual variation. © 2014 Elsevier Ltd.


Mikkelsen L.F.,Novo Nordisk AS | Mikkelsen L.F.,Center for Applied Laboratory Animal Research | Sorensen D.B.,Center for Applied Laboratory Animal Research | Sorensen D.B.,Copenhagen University | And 10 more authors.
Animal Welfare | Year: 2010

Since the release of the revised Appendix A from the Council of Europe for housing of laboratory animals there have been claims that laboratory animals should be housed under more complex conditions; known popularly as enrichment. A number of studies have expressed concerns that this may increase uncontrollable variation in the animals, thereby creating the need for greater numbers of animals. Within neurobiology there would appear to be a scientific basis for such concern. However, even though this may be used as an argument for denying the animal environmental enrichment, it is unclear whether there is any basis for concern within other research areas. The aim of this study, therefore, was to explore whether clinical pathology and cardiovascular parameters were influenced by housing rats under environmentally enriched conditions. Male, Sprague-Dawley rats were housed under three different regimes: non-enriched, standard-enriched (according to the guidelines of the Council of Europe) and extra-enriched with a shelf and higher cages. All housing forms were based upon commercially available, standardised equipment. A total of 41 different parameters were monitored via clinical pathology, telemetry and coagulation tests and virtually no differences were observed in relation to the manner in which the rats were housed. The uncontrollable variation observed in our study was compared to within-strain variation data supplied from the breeder and was relatively low in all three types of housing. We conclude, based upon our studies in male, Sprague-Dawley rats, that so far there is no basis for concern that enriched housing will lead to increased group sizes when using animals for research within this field and, as such, there is no reason not to enrich the environment of such rats. © 2010 Universities Federation for Animal Welfare.

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