 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 04, 2012 |
| Title |
A new mouse model for mania shares genetic correlates with human bipolar disorder. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
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.
|
| |
|
| Contributor(s) |
Saul MC, Gessay GM, Gammie SC |
| Citation(s) |
22675514 |
| Submission date |
May 20, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Michael C. Saul |
| E-mail(s) |
michael.saul@jax.org
|
| Organization name |
The Jackson Laboratory
|
| Lab |
Chesler Lab
|
| Street address |
600 Main St
|
| City |
Bar Harbor |
| State/province |
ME |
| ZIP/Postal code |
04609 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA141523 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29417_RAW.tar |
52.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...