Brain transcriptome analyses of paternal-specific mutant GRB10KO and potential insights into dominance behaviour

Abstract

Variation of gene expression in the brain may play a critical role in determining behavioural phenotypes. Grb10 gene is an imprinted gene expressed from embryonic stages into adulthood. In mice, Grb10 parental alleles are expressed in a tissue-specific manner, with the expression of the maternal allele in the placental trophoblasts and most embryonic tissues. The paternal allele is expressed in certain regions of the brain. Grb10 expression in the adult is limited to few tissues with the maternal allele expressed in muscle tissues and the paternal copy maintains its expression in the midbrain. While maternal knockdown of Grb10 is associated with foetal growth, a function shared with several other imprinted genes, knocking down of the paternal allele mice is associated with increased social dominance. The interactors of Grb10 in the brain, however, are not yet known. In this project, I aimed to uncover the potential molecular interactors mediating Grb10’s function in the brain.For this, I obtained whole genome transcriptional profiles using Illumina RNA-Seq technology for the midbrain where paternally inherited Grb10 is expressed in adult stages and the neocortex where Grb10 is not expressed for mutantGrb10KO+/p and wild-type. Using differential gene expression analyses, I identified a set of genes altered in the paternal mutant Grb10KO+/p. I further examined how these sets of genes change over time by examining samples taken at different developmental stages. Gene expression profile changes in the Grb10KO in the brain are distinct from gene expression changes in the liver suggesting that the maternal and paternal alleles are associated with different sets of genes in different tissues. Co-expression analyses revealed significant shifts in gene to gene relationships in the KO context. Together, my results provide insights into the molecular interactors of Grb10 in the brain and may give clues as to how Grb10 influences social dominance.

Date of Award	23 Aug 2018
Original language	English
Awarding Institution	University of Bath
Supervisor	Araxi Urrutia (Supervisor) & Andrew Ward (Supervisor)