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Physiol. Genomics 37: 249-259, 2009. First published March 17, 2009; doi:10.1152/physiolgenomics.90407.2008
1094-8341/09 $8.00
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Received 26 December 2008; accepted in final form 10 March 2009.
Physiological Genomics 37:249-259 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway

S. Kõks 1,2, U. Soomets 3, J. L. Paya-Cano 4, C. Fernandes 4, H. Luuk 1, M. Plaas 5, A. Terasmaa 1, V. Tillmann 6, K. Noormets 6, E. Vasar 1 and L. C. Schalkwyk 4

1 Department of Physiology, University of Tartu
2 Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences
3 Department of Biochemistry, University of Tartu, Tartu, Estonia
4 Social, Genetic and Developmental Psychiatry Centre (PO82), Institute of Psychiatry, King's College London, London, United Kingdom
5 Institute of Technology, University of Tartu, Tartu, Estonia
6 Department of Pediatrics, University of Tartu, Tartu, Estonia

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.

wolframin protein; knockout mice; oligonucleotide microarrays; congenic footprint






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