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Sex-dependent and strain-dependent gene liver gene expression

ABSTRACT: A series of dual-channel gene expression profiles obtained using Agilent Mouse TOE 75k microarrays was used to examine the sex-dependent differences in gene expression across three outbred mouse strains, 129J x Black Swiss, 129J x BALB/c, and ICR. This series is comprised of samples obtained from 3 pools of randomly chosen independent cDNA samples of male and female 129Jx BALB/c mice and 3 randomly chosen independent cDNA samples of male and female 129J x Black Swiss mice and 5 randomly chosen independent cDNA samples of male and female ICR mice. The ICR mice were randomly distributed into three and two member pools for each sex and two of the 5 samples for each sex were independently hybridized separately as well. Comparison of the sex-specific genes for the three outbred strains generated lists of strain-dependent and strain-independent sex-specific genes. Keywords: sex response and strain response

ORGANISM(S): Mus musculus

PROVIDER: GSE7170 | GEO | 2007/07/30

SECONDARY ACCESSION(S): PRJNA98259

REPOSITORIES: GEO

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Project description:Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes. In total, 12 total RNA samples were used for microarray analysis: 6 samples from Madison mice and 6 samples from ICR outbred mice. All samples were biological replicates.

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Sex-dependent and strain-dependent gene liver gene expression

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