Frataxin shows developmentally regulated tissue-specific expression in the mouse embryo

Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused either by an intronic GAA triplet repeat expansion that suppresses the expression of the frataxin gene on chromosome 9q13, or, rarely, by point mutations in the frataxin gene. We investigated the expression of the mouse frataxin homologue during embryonic development by Northern blot analysis and RNA in situ hybridization. Very faint expression could be detected from E10.5 in the neuroepithelium and more clearly from E12.5 in the developing central nervous system. At E14.5, frataxin was expressed at a much higher level that remained constant into the postnatal period. Maximum expression was observed in the spinal cord, particularly at the thoracolumbar level, and in the dorsal root ganglia. Significant levels of transcript could also be detected in the proliferating cells in the periventricular zone, in the cortical plates, in the heart, in the axial skeleton, and in some epithelial and mesenchymal tissues. Overall, the distribution of frataxin mRNA was in good accordance with previous data from Northern analysis of adult human tissues, the major discrepancy being the expression in mouse embryonic cerebral cortex which was not observed in adult human brain. The tissues expressing frataxin during development appear to be those that become dysfunctional or atrophied in FRDA. Overall, our data suggest that frataxin is a protein whose expression is cell-specific and developmentally regulated. (C) 1997 Academic Press.