Huntington's Disease by Bates Gillian; Jones Lesley; Tabrizi Sarah

Author:Bates, Gillian; Jones, Lesley; Tabrizi, Sarah
Language: eng
Format: epub
Publisher: Oxford University Press, Incorporated
Published: 2014-03-19T16:00:00+00:00

HTT EXPRESSION AND DISTRIBUTION

In both mice and humans, HTT is ubiquitously distributed, with the highest levels in neurons of the CNS and testis (Strong et al., 1993; Landwehrmeyer et al., 1995; Sharp et al., 1995; Bhide, 1996; Sapp et al., 1997; Vonsattel & DiFiglia, 1998). Two major HTT messenger RNAs (mRNAs) have been identified in humans and rodents that differ by 3 kb and are generated by alternative cleavage and polyadenylation of the primary transcript, producing a long and a short 3’-untranslated region (Lin et al., 1993; Lin et al., 1994). In both species the long-UTR transcript is predominantly expressed in the brain, whereas the short-UTR transcript is more widely expressed. Recent data demonstrate that the mutant HTT gene is also mis-spliced to generate a short polyadenylated mRNA that is translated into an exon 1 HTT protein (Sathasivam et al., 2013).

Analysis of HTT expression in mouse and human development have indicated that HTT is expressed from postfertilization stages (Dragatsis et al., 1998). HTT expression increases in parallel with the maturation of neurons in the postnatal period (Bhide et al., 1996). In support of these early observations, several recent studies have highlighted a critical role for the protein in brain development as well as in the adult brain. Evolutionary studies have reported that HTT expression in neuronal cells occurred during evolution. HTT is found predominantly in non-neural tissues in the echinoderm Heliocidaris herithrogramma (sea urchin), and it has a ubiquitous distribution in the primitive chordate Halocynthia roretzi (sea pineapple), with an increased level of expression in the nervous system (Kauffman et al., 2003). These studies indicate that the neural expression of the gene may be a chordate-specific trait. In line with these findings, HTT expression in the cephalochordate Branchiostoma floridae (amphioxus) shows increased expression in the nervous system and subregionalization and is the most ancestral part of the chordate phylogeny to show this (Candiani et al., 2007).

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.