Tissue-specific overexpression of the HSA21 gene GABPalpha: implications for DS.

The ETS transcription factor GABPalpha is encoded by a gene on HSA21 and interacts with an ankyrin repeat-containing beta subunit to form the GABP complex. GABP regulates expression of genes involved in mitochondrial respiration and neuromuscular signalling. When GABPalpha mRNA is overexpressed in human DS fibroblast cell lines, or by tranfection in NIH3T3 cells, no increase in protein level is detected. However, increased Gabpalpha gene dosage in the Ts65Dn segmental trisomy mouse model of DS (DS) results in elevated Gabpalpha protein levels in brain and skeletal muscle only. These findings suggest that GABPalpha protein levels are tightly regulated in a tissue-specific manner, and consequently GABP may play a role in DS pathologies in tissues where GABPalpha protein levels are elevated.