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Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging
BACKGROUND: Complex species-specific, developmental- and tissue-dependent mechanisms regulate alternative splicing of tau, thereby diversifying tau protein synthesis. The functional role of alternative splicing of tau e.g. exon 10 has never been examined in vivo, although genetic studies suggest tha...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222861/ https://www.ncbi.nlm.nih.gov/pubmed/24261309 http://dx.doi.org/10.1186/1471-2202-14-148 |
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author | Gumucio, Astrid Lannfelt, Lars Nilsson, Lars NG |
author_facet | Gumucio, Astrid Lannfelt, Lars Nilsson, Lars NG |
author_sort | Gumucio, Astrid |
collection | PubMed |
description | BACKGROUND: Complex species-specific, developmental- and tissue-dependent mechanisms regulate alternative splicing of tau, thereby diversifying tau protein synthesis. The functional role of alternative splicing of tau e.g. exon 10 has never been examined in vivo, although genetic studies suggest that it is important to neurodegenerative disease. RESULTS: Gene-targeting was used to delete exon 10 in murine tau on both alleles (E10−/−) to study its functional role. Moreover, mice devoid of exon 10 (E10+/−) on one allele were generated to investigate the effects of 1:1 balanced expression of 4R-/3R-tau protein, since equal amounts of 4R-/3R-tau protein are synthesized in human brain. Middle-aged E10−/− mice displayed sensorimotor disturbances in the rotarod when compared to age-matched E10+/− and wild-type mice, and their muscular grip strength was less than that of E10+/− mice. The performance of E10+/− mice and wild-type mice (E10+/+) was similar in sensorimotor tests. Cognitive abilities or anxiety-like behaviours did not depend on exon 10 in tau, and neither pathological inclusions nor gene-dependent morphological abnormalities were found. CONCLUSION: Ablation of exon 10 in the murine tau gene alters alternative splicing and tau protein synthesis which results in mild sensorimotor phenotypes with aging. Presumably related microtubule-stabilizing genes rescue other functions. |
format | Online Article Text |
id | pubmed-4222861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42228612014-11-07 Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging Gumucio, Astrid Lannfelt, Lars Nilsson, Lars NG BMC Neurosci Research Article BACKGROUND: Complex species-specific, developmental- and tissue-dependent mechanisms regulate alternative splicing of tau, thereby diversifying tau protein synthesis. The functional role of alternative splicing of tau e.g. exon 10 has never been examined in vivo, although genetic studies suggest that it is important to neurodegenerative disease. RESULTS: Gene-targeting was used to delete exon 10 in murine tau on both alleles (E10−/−) to study its functional role. Moreover, mice devoid of exon 10 (E10+/−) on one allele were generated to investigate the effects of 1:1 balanced expression of 4R-/3R-tau protein, since equal amounts of 4R-/3R-tau protein are synthesized in human brain. Middle-aged E10−/− mice displayed sensorimotor disturbances in the rotarod when compared to age-matched E10+/− and wild-type mice, and their muscular grip strength was less than that of E10+/− mice. The performance of E10+/− mice and wild-type mice (E10+/+) was similar in sensorimotor tests. Cognitive abilities or anxiety-like behaviours did not depend on exon 10 in tau, and neither pathological inclusions nor gene-dependent morphological abnormalities were found. CONCLUSION: Ablation of exon 10 in the murine tau gene alters alternative splicing and tau protein synthesis which results in mild sensorimotor phenotypes with aging. Presumably related microtubule-stabilizing genes rescue other functions. BioMed Central 2013-11-22 /pmc/articles/PMC4222861/ /pubmed/24261309 http://dx.doi.org/10.1186/1471-2202-14-148 Text en Copyright © 2013 Gumucio et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Gumucio, Astrid Lannfelt, Lars Nilsson, Lars NG Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title | Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title_full | Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title_fullStr | Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title_full_unstemmed | Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title_short | Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
title_sort | lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222861/ https://www.ncbi.nlm.nih.gov/pubmed/24261309 http://dx.doi.org/10.1186/1471-2202-14-148 |
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