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Open Access Highly Accessed Research article

Lack of exon 10 in the murine tau gene results in mild sensorimotor defects with aging

Astrid Gumucio1, Lars Lannfelt1 and Lars NG Nilsson12*

Author affiliations

1 Department of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden

2 Department of Pharmacology, Oslo University and Oslo University Hospital, Postboks 1057 Blindern, NO-0316 Oslo, Norway

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Citation and License

BMC Neuroscience 2013, 14:148  doi:10.1186/1471-2202-14-148

Published: 22 November 2013

Abstract

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.

Keywords:
Alzheimer’s disease; Tau; Knockout mice; Alternative splicing; Microtubule