Epsilon Open Archive

Abstract

Following advances in genetic engineering, mice are today the most commonly used mammal in research. This thesis addresses two issues: the impact on animal welfare and research quality by environmental enrichment and the characterization of genetically modified mice. In the first paper, the effects of environmental enrichment before weaning were studied. No alterations were found at age 4 weeks, but after 8 weeks of environmental enrichment the home cage activity had decreased. In the second paper, a battery of behavioural tests was used to characterize a spontaneous mouse mutant, the leaner heterozygous. This mutant showed cognitive and motor impairment. This finding was followed up, in the third paper, by housing the leaner heterozygous and wild type mice in cages with three different degrees of environmental complexity. In Morris watermaze tests at 6, 12 and 20 months of age, environmental enrichment was found to increase learning and memory capacity in mice of both genotypes. In paper IV, a characterization routine is presented for pre-weaning monitoring of mutant mice. Individual pups were scored for several development parameters on postnatal days 1, 3, 7 and 14. At weaning (day 19 to 21) a clinical examination and the novel cage test for emotional reactivity were carried out. The protocol was tested in several C57BL/6, BALB/C, 129S6 and B6CBAF1 litters. The characterization routine was efficient in detecting differences between genotypes in weight gain, physical condition at weaning, reaction to handling and emotional reactivity. In paper V, C57BL/6, 129S6 and B6CBAF1 mice were used. The mice were tested in the novel cage (at weaning), the open Field test (at 5 weeks), and from 9 weeks of age in the elevated plus-maze, the concentric square field and the rat exposure test. Results obtained with the novel cage test at weaning were largely consistent with those obtained in the established tests later in life. In conclusion, this thesis shows that cage enrichment decreases the cognitive deficits in the heterozygous leaner mouse. The new protocol for pre-weaning monitoring can be used to detect deviations in early development and emotional reactivity in a number of commonly used mice genotypes.