The effects of microchipping C57BL/6N mice on standard phenotyping tests

Abstract

The C57BL/6N inbred lines of mice are widely used in genetic research. They are particularly favoured in large scale studies such as the International Mouse Phenotyping Consortium (IMPC), where C57BL/6N mice are genetically altered to generate a collection of null alleles (currently more than 8500 null alleles have been generated). In this project, mice carrying null alleles are subjected to a pipeline of broad-based phenotyping tests to produce wide ranging phenotyping data on each model. We have previously described the development of a Home Cage Analysis system that automatically tracks the activity of group housed mice from a microchip inserted in the groin. This platform allows assessment of multiple biologically relevant phenotypes over long periods of time without experimenter interference, and therefore is particularly suited for high through-put studies. To investigate the impact of microchips on other tests carried out in the IMPC pipeline, we inserted microchips in 12 male and 12 female C57BL/6Ntac mice at seven weeks of age. Starting at nine weeks of age these mice underwent standard phenotyping tests, concurrently with 20 unchipped C57BL/6Ntac mice (10 females, 10 males). Tissues from a subset of the microchipped mice (six males and six females), chosen at random, were also sent for histopathological examination at the end of the phenotyping pipeline. No significant impact of insertion of microchip was observed in any of the phenotyping tests apart from bone mineral density measurement at DEXA due to the nature of the microchip. We therefore recommend that the microchip be inserted during the DEXA procedure, after the measurement is taken but before the mouse has recovered from the anaesthetic. This would avoid multiple anaesthetic exposures and prevent the potential variability in DEXA analysis output.

Keywords: C57BL/6NTac; Home cage analysis; Microchips; RFID; histopathology; mice; phenotyping.

Figure 1.

A) Bars represent average bone mineral density (g/cm ²) and average bone mineral content (g), for males and females as measured through dual-energy X-ray absorptiometry (DEXA). Microchipped females as well as males show a significant increase in the two parameters as compared to unchipped animals (n=10-12; ***p<0.001 and ****p<0.0001), the T bars represent ±sem. B) The lines represent average glucose concentration (mmol/L) over time as measured through IPGTT, the shapes represent average glucose concentration (mmol/L) for each group at that time point, the T bars represent ±sem. No statistically significant difference was seen in either sex for microchipped versus unchipped mice. C) The lines represent the body weight curve of the two treatment groups over time, the shapes represent mean body weight (gm) for each group at that time point, the T bars represent ±sem. No statistically significant difference was seen in either sex for microchipped versus unchipped mice.