Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/123739
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Type: Journal article
Title: Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau (mapta, maptb) gene transcripts
Author: Moussavi Nik, S.
Newman, M.
Ganesan, S.
Chen, M.
Martins, R.
Verdile, G.
Lardelli, M.
Citation: BMC Research Notes, 2014; 7(1):767-1-767-9
Publisher: BioMed Central
Issue Date: 2014
ISSN: 1756-0500
1756-0500
Statement of
Responsibility: 
Seyyed Hani Moussavi Nik, Morgan Newman, Swamynathan Ganesan, Mengqi Chen, Ralph Martins, Giuseppe Verdile and Michael Lardelli
Abstract: BACKGROUND: Microtubule-associated protein tau (MAPT) is abundant in neurons and functions in assembly and stabilization of microtubules to maintain cytoskeletal structure. Human MAPT transcripts undergo alternative splicing to produce 3R and 4R isoforms normally present at approximately equal levels in the adult brain. Imbalance of the 3R-4R isoform ratio can affect microtubule binding and assembly and may promote tau hyperphosphorylation and neurofibrillary tangle formation as seen in neurodegenerative diseases such as frontotemporal dementia (FTD) and Alzheimer's disease (AD). Conditions involving hypoxia such as cerebral ischemia and stroke can promote similar tau pathology but whether hypoxic conditions cause changes in MAPT isoform formation has not been widely explored. We previously identified two paralogues (co-orthologues) of MAPT in zebrafish, mapta and maptb. RESULTS: In this study we assess the splicing of transcripts of these genes in adult zebrafish brain under hypoxic conditions. We find hypoxia causes increases in particular mapta and maptb transcript isoforms, particularly the 6R and 4R isoforms of mapta and maptb respectively. Expression of the zebrafish orthologue of human TRA2B, tra2b, that encodes a protein binding to MAPT transcripts and regulating splicing, was reduced under hypoxic conditions, similar to observations in AD brain. CONCLUSION: Overall, our findings indicate that hypoxia can alter splicing of zebrafish MAPT co-orthologues promoting formation of longer transcripts and possibly generating Mapt proteins more prone to hyperphosphorylation. This supports the use of zebrafish to provide insight into the mechanisms regulating MAPT transcript splicing under conditions that promote neuronal dysfunction and degeneration.
Keywords: Microtubule-associated protein tau (MAPT); Alternative splicing; Alzheimer’s disease; Hypoxia; Zebrafish
Description: Published: 31 October 2014
Rights: © 2014 Moussavi Nik et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030015672
DOI: 10.1186/1756-0500-7-767
Appears in Collections:Genetics publications

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