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- W577466229 abstract "The key component of the Wnt/β-catenin pathway is β-catenin, a 780 amino acid proteinwhich was originally identified as a component of E-cadherin junctions, where it links E-cadherinwith α-catenin and consequently to the actin cytoskeleton. In the absence of Wnt signalling,cytoplasmic β-catenin is phosphorylated and subsequently degraded by ubiquitinylation.Activation of Wnt signalling stabilises cytoplasmic β-catenin, which translocates into the nucleuswhere it binds to nuclear transcription factors TCF/LEF and regulates the expression of over thirtygenes, including cell cycle activating genes.The Wnt/β-catenin pathway is essential for nervous system development and it isaberrantly active in common malignant tumours of the central nervous system, such asglioblastoma in adults and medulloblastoma in children.We have generated a mouse model expressing a Cre-recombinase-inducible form ofdegradation-resistant (oncogenic) β-catenin. We generated compound mutant mice to activatethe Wnt/β-catenin pathway in specific brain regions and during several developmental timepoints. Compound mutant transgenic mice expressed dominant active β-catenin in vivo, but didnot show developmental abnormalities or brain tumours even in combination with inactivated p53alleles. Similarly, neural stem cells expressing dominant active β-catenin did not show a growthadvantage or altered self-renewal. We attributed these results to low level expression of dominantactive β-catenin.In addition, we later acquired mice that carry an inducible deletion of the exon 3 of β-catenin (containing the phosphorylation site). Expression of this form of β-catenin did not increaseneural stem cell growth and self-renewal. However, in vivo expression results in brainmalformation and lethality depending on the cells in which β-catenin was activated, however,recombination in adult stem cells in vivo did not result in brain tumours." @default.
- W577466229 created "2016-06-24" @default.
- W577466229 creator A5010047435 @default.
- W577466229 date "2011-03-28" @default.
- W577466229 modified "2023-09-26" @default.
- W577466229 title "Generation and analysis of mouse models of aberrant β-catenin function" @default.
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