Gene Structure and Expression

Dorn Spinal Therapy

Spine Healing Therapy

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The FRDA locus is in the proximal long arm of chromosome 9 (Chamberlain et al. 1988). The gene contains seven exons spanning 95 kb of genomic DNA. It is transcribed in the cen-tel direction. The major, and probably only functionally relevant messenger RNA (mRNA), has a size of 1.3 kb, corresponding to the first five exons, numbered 1-5a. The encoded protein, predicted to contain 210 amino acids, was designated frataxin (Campuzano et al. 1996).

The gene is expressed in all cells, but at variable levels in different tissues and at different times during development (Campuzano et al. 1996; Jiraler-spong et al. 1997; Koutnikova et al. 1997). In adult humans, frataxin mRNA and protein are most abundant in the heart, brain and spinal cord, followed by liver, skeletal muscle, and pancreas. In mouse embryos, expression starts in the neuroepithelium at embryonic day 10.5 (E10.5), then reaches its highest level at E14.5 and into the postnatal period (Jiralerspong et al. 1997; Koutnikova et al. 1997). In developing mice, the highest levels of frataxin mRNA are found in the spinal cord, particularly at the thoracolumbar level, and in the DRG. The developing brain is also very rich in frataxin mRNA, which is abundant in the proliferating neural cells in the periventricular zone, in the cortical plates, and in the ganglionic eminence. Robust expression is also detected in the heart, in the axial skeleton, and in some epithelial (skin, teeth) and mesenchymal (brown fat) tissues (Jiralerspong et al. 1997; Koutnikova et al. 1997).

Overall, frataxin expression is generally higher in mitochondria-rich cells, such as cardiomyocytes and neurons. There is, however, a still-unexplained additional cell specificity, which in the nervous system is reflected in a higher abundance of frataxin in specific neuronal types, such as primary sensory neurons.

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