Title |
FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis
|
---|---|
Published in |
Acta Neuropathologica Communications, April 2015
|
DOI | 10.1186/s40478-015-0202-6 |
Pubmed ID | |
Authors |
Yoshihiro Kino, Chika Washizu, Masaru Kurosawa, Mizuki Yamada, Haruko Miyazaki, Takumi Akagi, Tsutomu Hashikawa, Hiroshi Doi, Toru Takumi, Geoffrey G Hicks, Nobutaka Hattori, Tomomi Shimogori, Nobuyuki Nukina |
Abstract |
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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Japan | 1 | <1% |
Unknown | 159 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 39 | 24% |
Student > Master | 23 | 14% |
Student > Bachelor | 21 | 13% |
Researcher | 15 | 9% |
Student > Doctoral Student | 7 | 4% |
Other | 21 | 13% |
Unknown | 35 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 36 | 22% |
Neuroscience | 34 | 21% |
Agricultural and Biological Sciences | 22 | 14% |
Medicine and Dentistry | 14 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
Other | 14 | 9% |
Unknown | 38 | 24% |