アイテム詳細

要旨

Organisms have evolved different behavioral strategies for better survival and reproduction. However, the genetic basis for such traits remains still as a longstanding fascinating question in evolutionary biology. Mate choice strategy is one of the behavioral traits which can play an important role in the life history of organisms. A previous study had shown that mate choice preference between two populations of the Western house mouse (M. m. domesticus) is influenced by the genetic background of the fathers. Transcriptome analysis in a follow up study revealed an imprinted cluster on Chromosome 7, known as Prader-Willi Syndrome (PWS) region, and also Peg13 on Chromosome 15 as loci that are highly differentiated between mouse populations and therefore have been suggested as potential regions which may regulate this paternal preference in the house mouse. The present thesis was aimed to investigate the functional role of these two imprinted regions in Western house mice behavior.
In the first chapter, I investigated the role of the PWS region on Chromosome 7 through a variety of techniques, including copy number variation analysis, behavioral correlations and transcriptomics. I found that two paternally imprinted tandemly repeated regulatory RNA coding genes (SNORD115 and SNORD116) are of special interest. Their copy number evolves very fast and correlates highly with personality traits between individuals. Further I found that the copy number variation influences the expression of more than 130 genes including genes involved in serotonin regulation, vocalization and bone development. The findings suggest a molecular mechanism for the generation and variability of personality traits in mammals.
The second chapter focuses on the analysis of paternally imprinted Peg13 gene, which has so far not been functionally studied. This gene has been known as non-coding gene, but data from ribosomal profiling analysis revealed that this gene could indeed produce a small peptide and it is not a simple non-coding gene. By using knock out mice, I showed even a partial deletion at 3’ part of Peg13 could significantly change expression of hundreds genes in the brain and could thus influence various mouse behaviors. The phenotypic analysis showed a significant effect on mouse sexual and parental behavior. Since RNAseq analysis from mouse brain development timeline showed that this gene has highest expression in day 12.5, I propose that Peg13 may play important role in preoptic area development with possible direct role in sexual and mate choice behavior.
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Overall the work presented in this thesis describes the first major molecular mechanism underlying mouse personality traits. It presents also the first functional study on the Peg13 gene in mice, which highlights its possible role in mouse brain development and sexual behavior.