Cristina Fillat

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Down's syndrome (DS) is a major cause of mental retardation, hypotonia and delayed development. Murine models of DS carrying large murine or human genomic fragments show motor alterations and memory deficits. The specific genes responsible for these phenotypic alterations have not yet been defined. DYRK1A, the human homolog of the Drosophila minibrain gene,(More)
We present a method to determine glucose 6-phosphate activity. This assay measures the rate of glucose released in the glucose-6-phosphatase reaction. The glucose is oxidized to beta-D-gluconolactone by glucose dehydrogenase in a coupled reaction that uses NAD(P)+. The determination is rapid, reproducible, and does not require withdrawal, precipitation,(More)
A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter(More)
Gene-directed enzyme prodrug therapy (GDEPT) is a two step therapeutic approach for cancer gene therapy. In the first step, the transgene is delivered into the tumor and expressed. In the second step a prodrug is administered and is selectively activated by the expressed enzyme. The first GDEPT system described was the thymidine kinase gene of the Herpes(More)
Down syndrome (DS) is the most common cause of mental retardation. Many neural phenotypes are shared between DS individuals and DS mouse models; however, the common underlying molecular pathogenetic mechanisms remain unclear. Using a transchromosomic model of DS, we show that a 30%-60% reduced expression of Nrsf/Rest (a key regulator of pluripotency and(More)
Most studies on TCF7L2 SNP variants in the pathogenesis of type 2 diabetes (T2D) focus on a role of the encoded transcription factor TCF4 in β cells. Here, a mouse genetics approach shows that removal of TCF4 from β cells does not affect their function, whereas manipulating TCF4 levels in the liver has major effects on metabolism. In Tcf7l2(-/-) mice, the(More)
The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency caused by mutations in the WASP gene. The disease is known to be associated with extensive clinical variability, and mutation studies indicate that genotypes are also highly variant among WAS patients. In this study, we performed mutation analysis of the WASP gene in 14 unrelated Spanish(More)
Stem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the(More)
The cognitive dysfunctions of Down Syndrome (DS) individuals are the most disabling alterations caused by the trisomy of human chromosome 21 (HSA21). In trisomic Ts65Dn mice, a genetic model for DS, the overexpression of HSA21 homologous genes has been associated with strong visuo-spatial cognitive alterations, ascribed to hippocampal dysfunction. In the(More)
Transgenic mice overexpressing Dyrk1A (TgDyrk1A), a Down syndrome (DS) candidate gene, exhibit motor and cognitive alterations similar to those observed in DS individuals. To gain new insights into the molecular consequences of Dyrk1A overexpression underlying TgDyrk1A and possibly DS motor phenotypes, microarray studies were performed. Transcriptome(More)