Abstract
To maximize the sensitivity of detecting affects of genetic variants in mice, variables have been minimized through the use of inbred mouse lines, by eliminating infectious organisms and controlling environmental variables. However, the impact of standard animal husbandry and experimental procedures on the validity of experimental data is under appreciated. In this study we monitored the impact of these procedures by using parameters that reflect stress and physiological responses to it. Short-term measures included telemetered heart rate and systolic arterial pressure, core body temperature and blood glucose, while longer-term parameters were assessed such as body weight. Male and female C57BL6/NTac mice were subjected to a range of stressors with different perceived severities ranging from repeated blood glucose and core temperature measurement procedures, intra-peritoneal injection and overnight fasting to cage transport and cage changing.Our studies reveal that common husbandry and experimental procedures significantly influence mouse physiology and behaviour. Systolic arterial pressure, heart rate, locomotor activity, core temperature and blood glucose were elevated in response to a range of experimental procedures. Differences between sexes were evident, female mice displayed more sustained cardiovascular responses and locomotor activity than male mice. These results have important implications for the design and implementation of multiple component experiments where the lasting effects of stress from previous tests may modify the outcomes of subsequent ones.
Highlights
Following the elucidation of the mouse genome sequence, comprehensive functional annotation of the mouse genome is pivotal to understanding the normal function of all genes and the mechanisms through which genetic variants cause disease
A gradual body weight (BW) gain was seen from day 5 post surgery, BW remained significantly reduced in implanted mice throughout the 14 day post operative period in comparison to the pre-operation weights
The data presented shows that common husbandry practices and experimental procedures can have a significant impact on mouse physiology and behaviour, as evidenced by profound and sustained increases in blood glucose (BG), Tc, locomotor and CV activity
Summary
Following the elucidation of the mouse genome sequence, comprehensive functional annotation of the mouse genome is pivotal to understanding the normal function of all genes and the mechanisms through which genetic variants cause disease. As the effort to generate mutant alleles for all mouse genes progresses with pace [1,2], the most facile and informative methods to elucidate phenotypes from knockout mice at large scale and high throughput remain a challenge [3]. The resource of targeted and gene trap alleles in the embryonic stem cell lines generated by members of the International Knockout Mouse Consortium (IKMC) provide a foundation of alleles on a uniform genetic background for large scale phenotyping programmes [4]. Several programmes have been initiated to generate and systematically phenotype the mice from these resources including the Sanger Mouse Genetics Project (MGP), European Mouse Disease Clinic (EUMODIC) and the International Mouse Phenotyping Consortium (IMPC) [5]. The phenotyping screens employed are designed to identify genes which perturb the function of the organism via
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