521 research outputs found
The Abcc6a knockout zebrafish model as a novel tool for drug screening for pseudoxanthoma elasticum
No full textHow sample handling distorts telomere studies
No full textTelomere length (TL) is investigated as a biomarker for aging and disease-susceptibility, but
measurement using quantitative polymerase chain reaction (qPCR) faces challenges in accuracy
and reproducibility. The potential impact of pre-analytical factors on TL measurements remains
underexplored. We evaluated the impact of delayed blood processing, a typical feature in population
studies. Blood samples from 35 adults were processed for buffy coat extraction either immediately or
kept at 4 °C and processed after three and seven days (total n=105). After processing, samples were
stored at -80 °C. Relative TL was measured via qPCR and expressed as T/S ratio. Strikingly, delayed
blood processing led to a significant increase in TL: the mean T/S ratio was 0.886±0.205 at day 0, rising
to 1.022±0.240 at day 3 (p=0.03) and to 1.190±0.205 at day 7 (p<0.001), corresponding to increases
of 15% and 34%, respectively. Notably, TL correlated inversely with DNA integrity. These findings
underscore the critical impact of delayed sample processing on TL measurements, emphasizing the
need for consistent pre-analytical protocols to ensure accurate and reliable research outcomes. The
impact of our findings is considerable as it may overshadow not only previously reported results but
also real biological differences in TL between studied groups of patients.This work is funded in part by the Research Foundation Flanders (grant number G072022N to JDB and grant
number 12X9623N to DSM)
Absence of arterial phenotype in mice with homozygous slc2A10 missense substitutions
No full textArterial tortuosity syndrome (ATS, MIM# 208050) is a rare autosomal recessive connective tissue disease, mainly characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries (Callewaert et al., 2008, Hum Mutat 29:150-158). Recently, mutations were identified in the SLC2A10 gene encoding the facilitative glucose transporter GLUT10 (Coucke et al., 2006, Nat Genet 38:452-457). It was hypothesized that loss-of-function of the transporter results in upregulation of the transforming growth factor beta (TGF beta) signaling pathway (Coucke et al., 2006, Nat Genet 38:452-457). We anticipated that a mouse model would help to gain more insight in the complex pathophysiological mechanism of human ATS. Here, we report that two mouse models, homozygous respectively for G128E and S150F missense substitutions in glut10 do not present any of the vascular, anatomical, or immunohistological abnormalities as encountered in human ATS patients. We conclude that these mouse strains do not phenocopy human ATS and cannot help the further elucidation of pathogenetic mechanisms underlying this disease
Molecular characterization of heritable connective tissuedisorders affecting bone and arteries.
No full textAnimal disease modeling of the arterial tortuosity syndrome : advancing the CRISPR/Cas9 system for improved genome editing
No full textSevere congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1
No full textContains fulltext :
136809.pdf (Publisher’s version ) (Closed access)Autosomal recessive cutis laxa (ARCL) type 2 constitutes a heterogeneous group of diseases mainly characterized by lax and wrinkled skin, skeletal anomalies, and a variable degree of intellectual disability. ALDH18A1-related ARCL is the most severe form within this disease spectrum. Here we report on the clinical and molecular findings of two affected individuals from two unrelated families. The patients presented with typical features of de Barsy syndrome and an overall progeroid appearance. However, the phenotype was highly variable including cardiovascular involvement in the more severe case. Investigation of a skin biopsy of one patient revealed not only the typical alterations of elastic fibers, but also an altered structure of mitochondria in cutaneous fibroblasts. Using conventional sequencing and copy number analysis we identified a frameshift deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene, respectively, in a homozygous state in both patients. Expression analysis in dermal fibroblasts from the patient carrying the microdeletion showed an almost complete absence of the ALDH18A1 mRNA resulting in an absence of the ALDH18A1 protein. So far, only 13 affected individuals from seven unrelated families suffering from ALDH18A1-related cutis laxa have been described in literature. Our findings provide new insights into the clinical spectrum and show that beside point mutations microdeletions are a possible cause of ALDH18A1-ARCL
Ontwikkeling van een merkersysteem bij studie van differentiatie in callus van Hordeum vulgare L.
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