Whole chromosome aneuploidy in the brain of Bub1bH/H and Ercc1-/{Delta}7 mice
High levels of aneuploidy have been observed in disease-free tissues, including post-mitotic tissues such as the brain. Using a quantitative interphase-fluorescence in situ hybridization approach, we previously reported a chromosome-specific, age-related increase in aneuploidy in the mouse cerebral cortex. Increased aneuploidy has been associated with defects in DNA repair and the spindle assembly checkpoint, which in turn can lead to premature aging. Here, we quantified the frequency of aneuploidy of three autosomes in the cerebral cortex and cerebellum of adult and developing brain of Bub1bH/H mice, which have a faulty m...
Source: Human Molecular Genetics - February 5, 2016 Category: Genetics & Stem Cells Authors: Andriani, G. A., Faggioli, F., Baker, D., Dolle, M. E. T., Sellers, R. S., Hebert, J. M., Van Steeg, H., Hoeijmakers, J., Vijg, J., Montagna, C. Tags: ARTICLES Source Type: research
The apical ectodermal ridge of the mouse model of ectrodactyly Dlx5;Dlx6-/- shows altered stratification and cell polarity, which are restored by exogenous Wnt5a ligand
The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5–DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double knockout (DKO) of Dlx5 and Dlx6. During limb development, the apical ectodermal ridge (AER) is a key-signaling center responsible for early proximal–distal growth and patterning. In Dlx5;6 DKO hindlimbs, the central wedge of the AER loses multilayered organization and shows down-regulation of FGF8...
Source: Human Molecular Genetics - February 5, 2016 Category: Genetics & Stem Cells Authors: Conte, D., Garaffo, G., Lo Iacono, N., Mantero, S., Piccolo, S., Cordenonsi, M., Perez-Morga, D., Orecchia, V., Poli, V., Merlo, G. R. Tags: ARTICLES Source Type: research
Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus enhances anxiety-related behaviour
The brain-specific miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 domain is implicated in several aspects of brain development and function, particularly in fine-tuning the dendritic outgrowth and spine remodelling of hippocampal neurons. Whether it might influence behaviour and memory-related processes has not yet been explored at the whole organism level. We previously reported that constitutive deletion of the miR-379/miR-410 gene cluster affects metabolic adaptation in neonatal mice. Here, we examined the role of this cluster in adult brain functions by subjecting mice with the constitutive deletion to a batte...
Source: Human Molecular Genetics - February 5, 2016 Category: Genetics & Stem Cells Authors: Marty, V., Labialle, S., Bortolin-Cavaille, M.-L., Ferreira De Medeiros, G., Moisan, M.-P., Florian, C., Cavaille, J. Tags: ARTICLES Source Type: research
Combined use of Saccharomyces cerevisiae, Caenorhabditis elegans and patient fibroblasts leads to the identification of clofilium tosylate as a potential therapeutic chemical against POLG-related diseases
Mitochondria are organelles that have their own DNA (mitochondrial DNA, mtDNA) whose maintenance is necessary for the majority of ATP production in eukaryotic cells. Defects in mtDNA maintenance or integrity are responsible for numerous diseases. The DNA polymerase (POLG) ensures proper mtDNA replication and repair. Mutations in POLG are a major cause of mitochondrial disorders including hepatic insufficiency, Alpers syndrome, progressive external ophthalmoplegia, sensory neuropathy and ataxia. Mutations in POLG are also associated with parkinsonism. To date, no effective therapy is available. Based on the conservation of...
Source: Human Molecular Genetics - February 5, 2016 Category: Genetics & Stem Cells Authors: Pitayu, L., Baruffini, E., Rodier, C., Rötig, A., Lodi, T., Delahodde, A. Tags: ARTICLES Source Type: research
Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division
Mitochondria are dynamic organelles that divide and fuse by remodeling an outer and inner membrane in response to developmental, physiological and stress stimuli. These events are coordinated by conserved dynamin-related GTPases. The dynamics of mitochondrial morphology require coordination with mitochondrial DNA (mtDNA) to ensure faithful genome transmission, however, this process remains poorly understood. Mitochondrial division is linked to the segregation of mtDNA but how it affects cases of mtDNA heteroplasmy, where two or more mtDNA variants/mutations co-exist in a cell, is unknown. Segregation of heteroplasmic human...
Source: Human Molecular Genetics - February 5, 2016 Category: Genetics & Stem Cells Authors: Jokinen, R., Marttinen, P., Stewart, J. B., Neil Dear, T., Battersby, B. J. Tags: ARTICLES Source Type: research
