Human Molecular Genetics, 2001, Vol. 10, No. 26 3083-3091
© 2001 Oxford University Press
The Leri–Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator
Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri–Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have established a cell culture model consisting of four stably transfected cell lines and analysed the functional properties of the SHOX protein on a molecular level. Results show that the SHOX-encoded protein is located exclusively within the nucleus of a variety of cell lines, including U2Os, HEK293, COS7 and NIH 3T3 cells. In contrast to this cell-type independent nuclear translocation, the transactivating potential of the SHOX protein on different luciferase reporter constructs was observed only in the osteogenic cell line U2Os. Since C-terminally truncated forms of SHOX lead to LWS and idiopathic short stature, we have compared the activity of wild-type and truncated SHOX proteins. Interestingly, C-terminally truncated SHOX proteins are inactive with regards to target gene activation. These results for the first time provide an explanation of SHOX-related phenotypes on a molecular level and suggest the existence of qualitative trait loci modulating SHOX activity in a cell-type specific manner.
+ To whom correspondence should be addressed. Tel: +49 6221 565059; Fax: +49 6221 565332; Email: gudrun_rappold@med.uni-heidelberg.de The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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