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Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and(More)
Diseases affecting motor neurons, such as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary spastic paraplegia and spinal bulbar muscular atrophy (Kennedy's disease) are a heterogeneous group of chronic progressive diseases and are among the most puzzling yet untreatable illnesses. Over the last decade, identification of mutations in genes(More)
Spinocerebellar ataxia type 3 is caused by the expansion of the coding CAG repeat in the ATXN3 gene. Interestingly, a -1 bp frameshift occurring within an (exp)CAG repeat would henceforth lead to translation from a GCA frame, generating polyalanine stretches instead of polyglutamine. Our results show that transgenic expression of (exp)CAG ATXN3 led to -1(More)
Restless legs syndrome (RLS) is a frequent sleep disorder that is linked to disturbed iron homeostasis. Genetic studies identified MEIS1 as an RLS-predisposing gene, where the RLS risk haplotype is associated with decreased MEIS1 mRNA and protein expression. We show here that RNA interference treatment of the MEIS1 worm orthologue increases ferritin(More)
Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate-limiting and initiating role in the(More)
OBJECTIVE To test the association between Tourette syndrome (TS) and genetic variants in genomic loci MEIS1, MAP2K5/LBXCOR1, and BTBD9, for which genome-wide association studies in restless legs syndrome and periodic limb movements during sleep revealed common risk variants. DESIGN Case-control association study. SETTING Movement disorder clinic in(More)
BACKGROUND Machado-Joseph disease is the most frequent dominant ataxia worldwide. Despite its frequency and presence in many populations, only 2 founder mutations have been suggested to explain its current geographic distribution. OBJECTIVES To trace back in history the main mutational events in Machado-Joseph disease, we aimed to assess ancestral(More)
BACKGROUND Notch signalling regulates neuronal differentiation in the vertebrate nervous system. In addition to a widespread function in maintaining neural progenitors, Notch signalling has also been involved in specific neuronal fate decisions. These functions are likely mediated by distinct Notch ligands, which show restricted expression patterns in the(More)
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild type or the expanded form of human PABPN1, and transgenic(More)