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| Status |
Public on Nov 02, 2011 |
| Title |
Hypothalamic gene expression profile indicates a reduction in G-protein signaling in the wfs1 mutant mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
WFS1 gene is coding protein with unknown function but its functional deficiency causes different neuropsychiatric and neuroendocrine syndromes. In the present study we aimed to find the functional networks influenced by the Wfs1 deficiency in the hypothalamus. We performed gene expression profiling (Mouse Gene 1.0 ST Arrays) in Wfs1 deficient mice (ko). Modified t-statistics was used for comparison of groups (wt vs ko). Functional annotation of the alterations in RNA levels was performed with Ingenuity Pathway Analysis. 305 genes were differentially expressed with nominal p-value less than 0.01. FDR adjusted p-values were significant (0.007) only for two genes – C4b (t=9.66) and Wfs1 (t=-9.03). However, several genes related to the G-protein signalling were very close to the FDR adjusted significance. For instance, Rgs4 (regulator of G-protein signalling 4) was down-regulated (-0.34, t=-5.4) in Wfs1 deficient mice. Changes in Rgs4 and C4B expression were confirmed by QRT-PCR. In humans, Rgs4 is in the locus for bipolar disease (BPD) and its expression is down-regulated in BPD. C4b is the gene related to the neurodegenerative diseases. In conclusion, hypothalamic gene expression profiling indicates alterations in some functionally relevant molecular pathways explaining the clinical syndrome in the Wolfram syndrome patients.
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| Overall design |
18 samples, two genotypes (wild type and mutant), in 129S6 genetic background
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| Contributor(s) |
Koks S, Soomets U, Fernandes C, Plaas M, Terasmaa A, Tillmann V, Noormets K, Vasar E, Schalkwyk LC |
| Citation(s) |
22028430 |
| Submission date |
Nov 01, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Sulev Koks |
| E-mail(s) |
sulev.koks@murdoch.edu.au
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| Phone |
+61864570313
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| Organization name |
Murdoch University
|
| Department |
Centre for Molecular Medicine and Innovative Therapeutics
|
| Street address |
90 South Street
|
| City |
Perth |
| State/province |
Western Australia |
| ZIP/Postal code |
6150 |
| Country |
Australia |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA149013 |
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