FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis

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dc.contributor.authorKino, Yoshihiro
dc.contributor.authorWashizu, Chika
dc.contributor.authorKurosawa, Masaru
dc.contributor.authorYamada, Mizuki
dc.contributor.authorMiyazaki, Haruko
dc.contributor.authorAkagi, Takumi
dc.contributor.authorHashikawa, Tsutomu
dc.contributor.authorDoi, Hiroshi
dc.contributor.authorTakumi, Toru
dc.contributor.authorHicks, Geoffrey G
dc.contributor.authorHattori, Nobutaka
dc.contributor.authorShimogori, Tomomi
dc.contributor.authorNukina, Nobuyuki
dc.date.accessioned2015-10-08T17:55:29Z
dc.date.available2015-10-08T17:55:29Z
dc.date.issued2015-04-25
dc.date.updated2015-10-06T22:53:57Z
dc.description.abstractAbstract Introduction FUS/TLS is an RNA-binding protein whose genetic mutations or pathological inclusions are associated with neurological diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and essential tremor (ET). It is unclear whether their pathogenesis is mediated by gain or loss of function of FUS/TLS. Results Here, we established outbred FUS/TLS knockout mice to clarify the effects of FUS/TLS dysfunction in vivo. We obtained homozygous knockout mice that grew into adulthood. Importantly, they did not manifest ALS- or ET-like phenotypes until nearly two years. Instead, they showed distinct histological and behavioral alterations including vacuolation in hippocampus, hyperactivity, and reduction in anxiety-like behavior. Knockout mice showed transcriptome alterations including upregulation of Taf15 and Hnrnpa1, while they have normal morphology of RNA-related granules such as Gems. Conclusions Collectively, FUS/TLS depletion causes phenotypes possibly related to neuropsychiatric and neurodegenerative conditions, but distinct from ALS and ET, together with specific alterations in RNA metabolisms.
dc.identifier.citationActa Neuropathologica Communications. 2015 Apr 25;3(1):24
dc.identifier.urihttp://dx.doi.org/10.1186/s40478-015-0202-6
dc.identifier.urihttp://hdl.handle.net/1993/30891
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderKino et al.; licensee BioMed Central.
dc.titleFUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis
dc.typeJournal Article
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