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Since the discovery of the Huntington’s Disease (HD) gene (Huntington's Disease Collaborative Research Group, 1993) various research groups have aimed to discover the subcellular and tissue distribution of its mRNA and protein. The human HD gene is expressed ubiquitously in all human tissues as two major messenger RNA (mRNA) transcripts, 13.6 kb and 10.3 kb in length, which differ in the size of their 3’ UTRs due to differential polyadenylation (Trottier et al., 1995). HD mRNA is expressed in both neural and non-neural tissues with high levels of expression in brain and testis (Sharp et al. 1995; Strong et al. 1993). Northern blot and in situ hybridization analyses indicate that the two transcripts are expressed in many human tissues (heart, kidney, lungs, pancreas, muscles, liver, placenta) with higher expression of the longer transcript in the brain (Strong et al., 1993; Sharp et al., 1995). In the brain, highest levels were found in cerebral cortex and cerebellum, intermediate levels in the hippocampus and the lowest levels in the caudate nucleus and thalamus (Li et al., 1993). In addition to this, neuronal expression predominates over glial expression (Strong et al., 1993). No difference in the mRNA expression pattern between HD brains and controls was reported (Landwehrmeyer et al., 1995). The HD gene encodes a protein of 3144 amino acids with a molecular mass of 348 kDa, termed huntingtin (htt). The polyQ tract starts at residue 18 and is followed by a stretch of prolines. Similar to RNA studies, protein studies also indicate ubiquitous expression of htt in a variety of cells and tissues throughout the development and in the adult (Zeitlin et al., 1995) in both brain and peripheral tissue (Hoogeveen et al., 1993; Jou and Myers, 1995; Sharp et al., 1995). Normal huntingtin is widely distributed in the body, with the highest levels in the brain and testis. In HD patients, normal and mutant huntingtin have similar distribution and expression patterns (Sharp et al., 1995; Trottier et al., 1995). |
