Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice

S. Kõks; U. Soomets; M. Plaas; A. Terasmaa; K. Noormets; V. Tillmann; E. Vasar; C. Fernandes; L.C. Schalkwyk

doi:10.1152/physiolgenomics.00117.2011

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Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice

S. Kõks, U. Soomets, M. Plaas, A. Terasmaa, K. Noormets, V. Tillmann, E. Vasar, C. Fernandes and L.C. Schalkwyk

Physiological Genomics, Vol.43(24), pp.1351-1358

2011

DOI: https://doi.org/10.1152/physiolgenomics.00117.2011

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Abstract

The Wfs1 gene codes for a protein with unknown function, but deficiency in this protein results in a range of neuropsychiatric and neuroendocrine syndromes. In the present study we aimed to find the functional networks influenced by Wfs1 in the hypothalamus. We performed gene expression profiling (Mouse Gene 1.0 ST Arrays) in Wfs1-deficient mice; 305 genes were differentially expressed with nominal P value < 0.01. FDR (false discovery rate)-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 G protein signaling were very close to the FDR-adjusted significance level, such as Rgs4 (regulator of G protein signaling 4) that was downregulated (−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 downregulated in BPD. C4b is a gene related to the neurodegenerative diseases. Functional analysis including the entire data set revealed significant alterations in the canonical pathway “G protein-coupled receptor signaling.” The gene expression profile in the hypothalami of the Wfs1 mutant mice was significantly similar to the profiles of following biological functions: psychological disorders, bipolar disorder, mood disorder. In conclusion, hypothalamic gene expression profile resembles with some molecular pathways functionally related to the clinical syndromes in the Wolfram syndrome patients.

Details

Title: Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice
Authors/Creators: S. Kõks (Author/Creator) - University of Tartu
U. Soomets (Author/Creator) - Department of Physiology,
M. Plaas (Author/Creator)
A. Terasmaa (Author/Creator) - Department of Physiology,
K. Noormets (Author/Creator) - University of Tartu
V. Tillmann (Author/Creator) - University of Tartu
E. Vasar (Author/Creator) - Department of Physiology,
C. Fernandes (Author/Creator) - Social Genetic & Developmental Psychiatry
L.C. Schalkwyk (Author/Creator) - Social Genetic & Developmental Psychiatry
Publication Details: Physiological Genomics, Vol.43(24), pp.1351-1358
Publisher: American Physiological Society
Identifiers: 991005546349607891
Copyright: © 2011 the American Physiological Society
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.25 Molecular & Cell Biology - Cancer, Autophagy & Apoptosis; 1.25.1406 Unfolded Protein Response
Web Of Science research areas: Cell Biology; Genetics & Heredity; Physiology
ESI research areas: Molecular Biology & Genetics