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The glucocorticoid receptor (GR) belongs to the nuclear hormone receptor superfamily. and acts as a transcription factor regulating approximately 20% of the entire human genome. As such, the GR plays important regulatory roles in a diverse number of physiological processes. including metabolism, development. neurobiology and immunity. The organism of choice for this study was, the pig (Sus scrofa as it is an excellent model organism for both the study of human disease (both - are similar size and physiology) and from an agricultural standpoint with fatness and maternal aggression traits of interest in both disciplines. Excess fat in the body can cause many conditions including heart disease, stroke and cancer and forms a commercially important trait due to market preferences for different fat levels in the meat. Maternal aggression is a condition where sows bite and kill their offspring within 24 hours of birth. This is commercia1ly important as after an aggressive episode the sow is generally slaughtered resulting in a cost to the breeding companies. This condition also forms a model for human puerperal psychosis an extreme form of postnatal depression. This aim of this thesis was to identify a relationship between the GR and fatness and maternal aggression respectively, specifically: • To perform a Genome Wide Association Study to identify candidate genes involved in porcine maternal aggression and identify a role for the GR and its associated proteins in the onset of porcine maternal infanticide. 53 candidate genes were identified seven of which were related to the GR. • To further characterise the porcine GR gene via isolation of SNPs implicated in maternal aggression and/or fatness and to identify individual promoter combinations in the 5' UTR of the GR in 14 multiple tissues. A SNP repertoire of the porcine GR gene was produced. No SNPs showed an association with the phenotypes in question. RACE was unable to amplify first exion transcripts. To analyse the in vitro transcriptomic changes associated with the activation of the GR gene to dexamethasone and to identify the biological pathways involved. A full optional profile of the effects of the GR on porcine kidney cells in vitro was generated. To isolate key pathways involved in both maternal aggression and lipid deposition to determine whether dex activitation plays a key role in these phenotypes. Candidate genes and pathways were identified for both phenotypes with specific reference to NO synthesis, serotonin and CRH signalling for maternal aggression. These studies provide further insight into of the actions of the GR in vitro along with its role in the onset of porcine maternal aggression and fatness, potentially benefiting both human hea1th and animal breeding programs. |
