Dataset Information

Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via ?-catenin.

ABSTRACT: Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that ?-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by ?-catenin is well documented. Therefore, we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice showed a microcephaly-like phenotype with a reduced volume in the dentate gyrus (DG) and low levels of learning and memory, as evaluated using Morris water maze analysis and passive avoidance, respectively. Golgi staining revealed shorter dendrites, less dendritic complexity and decreased spine density in the DG of BCAS2 cKO mice. Moreover, the cKO mice displayed a short dendrite length in newborn neurons labeled by DCX, a marker of immature neurons, and BrdU incorporation. To further examine the mechanism underlying BCAS2-mediated dendritic malformation, we overexpressed ?-catenin in BCAS2-depleted primary neurons and found that the dendritic growth was restored. In summary, BCAS2 is an upstream regulator of ?-catenin gene expression and plays a role in dendrite growth at least partly through ?-catenin.

SUBMITTER: Huang CW

PROVIDER: S-EPMC5054673 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin.

Huang Chu-Wei CW Chen Yi-Wen YW Lin Yi-Rou YR Chen Po-Han PH Chou Meng-Hsuan MH Lee Li-Jen LJ Wang Pei-Yu PY Wu June-Tai JT Tsao Yeou-Ping YP Chen Show-Li SL

Scientific reports 20161007

Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that β-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by β-catenin is well documented. Therefore, we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice showed a microcephal ...[more]

PMID: 27713508

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Project description:Simple Summary ATRX and DAXX mutations occur in 30–40% of pancreatic neuroendocrine tumours (PanNETs), and there are no reports in the literature of any genetically engineered mouse model (GEMM) evaluating the effect of Atrx disruption as a putative driver event on PanNET initiation. We created a novel GEMM with Atrx conditional disruption in β cells. We observed that this genetic alteration, per se, was not tumourigenic, but we reported novel roles of Atrx on endocrine function, which resulted in dysglycaemia and the exacerbation of inflammageing (increased pancreatic inflammation and hepatic steatosis). Abstract ATRX is a chromatin remodeller that maintains telomere homeostasis. Loss of ATRX is described in approximately 10% of pancreatic neuroendocrine tumours (PanNETs) and associated with poorer prognostic features. Here, we present a genetically engineered mouse model (GEMM) addressing the role of Atrx loss (AtrxKO) in pancreatic β cells, evaluating a large cohort of ageing mice (for up to 24 months (mo.)). Atrx loss did not cause PanNET formation but rather resulted in worsening of ageing-related pancreatic inflammation and endocrine dysfunction in the first year of life. Histopathological evaluation highlighted an exacerbated prevalence and intensity of pancreatic inflammation, ageing features, and hepatic steatosis in AtrxKO mice. Homozygous floxed mice presented hyperglycaemia, increased weights, and glucose intolerance after 6 months, but alterations in insulinaemia were not detected. Floxed individuals presented an improper growth of their pancreatic endocrine fraction that may explain such an endocrine imbalance. A pilot study of BRACO-19 administration to AtrxKO mice resulted in telomere instability, reinforcing the involvement of Atrx in the maintenance of β cell telomere homeostasis. Thereby, a non-obese dysglycaemic GEMM of disrupted Atrx is here presented as potentially useful for metabolic studies and putative candidate for inserting additional tumourigenic genetic events.

Dataset Information

Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via ?-catenin.

Publications

Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin.

Similar Datasets

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