Journal article
Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway
Physiological Genomics, Vol.37(3), pp.249-259
2009
Abstract
The aim of present study was to describe changes in gene expression in the temporal lobe of mice induced by deletion of the Wfs1 gene. Temporal lobes samples were analyzed using Affymetrix Mouse Genome 420 2 GeneChips and expression profiles were functionally annotated with GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 ± 1.6 g) than their wild-type counterparts (31.0 ± 0.6 g, P < 0.0001). This difference existed in 129S6 and C57B6 backgrounds. Interestingly, microarray analysis identified upregulation of growth hormone (GH) transcripts and functional analysis revealed activation of GH pathways. In line with microarray data, the level of IGF-1 in the plasma of Wfs1 mutant mice was significantly increased (P < 0.05). Thus, Wfs1 deletion induces growth retardation, whereas the GH pathway is activated. To test the interaction between the Wfs1 deletion and genomic background, mutant mice were backcrossed to two different genetic backgrounds. In line with previous studies, an interaction between a gene knockout and genetic background was found in gene expression profiles in the congenic region. However, genetic background did not alter the effect of the Wfs1 mutation on either body weight or GH pathway activation. Further studies are needed to describe biochemical and molecular changes of the growth hormone axis as well as in other hormones to clarify their role in growth retardation in the Wfs1 mutant mice.
Details
- Title
- Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway
- Authors/Creators
- S. Kõks (Author/Creator)U. Soomets (Author/Creator)J.L. Paya-Cano (Author/Creator)C. Fernandes (Author/Creator)H. Luuk (Author/Creator)M. Plaas (Author/Creator)A. Terasmaa (Author/Creator)V. Tillmann (Author/Creator)K. Noormets (Author/Creator)E. Vasar (Author/Creator)L.C. Schalkwyk (Author/Creator)
- Publication Details
- Physiological Genomics, Vol.37(3), pp.249-259
- Publisher
- American Physiological Society
- Identifiers
- 991005540444207891
- Copyright
- © 2009 the American Physiological Society
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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