A5066973134- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Down syndrome and intellectual disability research
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Cosmology and Gravitation Theories
- Relativity and Gravitational Theory
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Diffusion and Search Dynamics
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Pulsars and Gravitational Waves Research
- Functional Brain Connectivity Studies
- Black Holes and Theoretical Physics
- Neuroscience and Neuropharmacology Research
- Stochastic processes and statistical mechanics
- Quantum Mechanics and Applications
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- RNA regulation and disease
- Molecular Biology Techniques and Applications
Université de Strasbourg
2011-2025
Institut de génétique et de biologie moléculaire et cellulaire
2015-2025
Centre National de la Recherche Scientifique
2011-2025
Inserm
2014-2025
Institut de Biologie Moléculaire et Cellulaire
2019-2022
Institut National de Recherche en Santé Publique
2019
Institut Clinique de la Souris
2011
Sorbonne Université
2006-2011
Laboratoire de Physique Théorique de la Matière Condensée
2009-2011
Laboratoire d’Etudes du Rayonnement et de la Matière en Astrophysique et Atmosphères
2006-2009
Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and caused by three copies of human chromosome 21. Mouse models are widely used better understand physiopathology in DS or test new therapeutic approaches. The older mouse trisomic Ts65Dn Ts1Cje mice. They display deficits similar those observed people, such as behavior cognition neuronal abnormalities. model currently for further assessment candidate drugs. In both models, trisomy was induced...
The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; reciprocal effects on the body mass index, head circumference brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a (Del/+) or (Dup/+) of Sult1a1-Spn region homologous to human locus. On C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight impaired adipogenesis, hyperactivity, repetitive...
The family of WD40-repeat (WDR) proteins is one the largest in eukaryotes, but little known about their function brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact neuronal morphology when inactivated mice. Remarkably, all seven showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b Wdr89), or absent (Wdr47), revealing common role for connectivity. We focused on poorly studied WDR47 protein sharing structural...
ABSTRACT Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). The understanding genotype–phenotype relationships, the identification driver genes and various proofs concept for therapeutics have benefited from mouse models. premier model, named Ts(1716)65Dn/J (Ts65Dn), displayed phenotypes related to DS features. It carries an additional minichromosome with Mir155 Zbtb21 region 16, homologous Hsa21, encompassing around 90 genes, fused centromeric part 17 Pisd-ps2/Scaf8...
We present a theoretical model of facilitated diffusion proteins in the cell nucleus. This model, which takes into account successive binding and unbinding events to DNA, relies on fractal description chromatin has been recently evidenced experimentally. Facilitated is shown quantitatively be favorable for fast localization target locus by transcription factor even enable minimization search time tuning affinity with DNA. study shows robustness mechanism, invoked so far only linear conformations
In this paper, we introduce a general computation method to systematically determine the mean first-passage time (MFPT), global (GMFPT) and splitting probabilities for continuous Brownian motion in confined 2D or 3D domain with multiple absorbing targets bulk on boundary. This is applied spherically symmetric domains limit of small-sized asymptotic expansions MPFT, GMFPT are obtained four distinct cases: bulk, boundary, approach gives unified description existing exact results which were...
Down syndrome is a common genetic disorder caused by trisomy of chromosome 21. Brain development in affected foetuses might be improved through prenatal treatment. One potential target DYRK1A, multifunctional kinase encoded 21 that, when overexpressed, alters neuronal excitation-inhibition balance and increases GAD67 interneuron density. We used green tea extract enriched EGCG to inhibit DYRK1A function only during gestation transgenic mice overexpressing Dyrk1a (mBACtgDyrk1a). Adult treated...
A copy-number variant (CNV) of 16p11.2 encompassing 30 genes is associated with developmental and psychiatric disorders, head size, body mass. The genetic mechanisms that underlie these associations are not understood. To determine the influence on development, we investigated effects CNV craniofacial structure in humans model organisms. We show deletion duplication have "mirror" specific features conserved between human rodent models CNV. By testing dosage individual shape mandible...
Abstract Background Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, deletion 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted implication Kctd13 genetic imbalance through regulation RHOA pathway. Methods Here, we generated a new mouse model small two key exons Kctd13. Then, targeted pathway to rescue cognitive phenotypes models pure...
Down syndrome (DS) is the most common genetic form of intellectual disability caused by presence an additional copy human chromosome 21 (Hsa21). To provide novel insights into genotype-phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging and hippocampal gene expression to screen several DS mouse models for 16 region homologous Hsa21. First, unravelled interactions between different regions how they contribute significantly altering outcome phenotypes in...
A new, wide class of relativistic stochastic processes is introduced. All considered so far in the literature are members this class. For each process, equations motion obtained an arbitrary Lorentz frame. The associated Kolmogorov equation also derived for first time, both (3+1)- and manifestly covariant forms.
Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The caused either microdeletions in the 17q21.31 chromosomal region or variants KANSL1 gene. reciprocal microduplication associated with psychomotor delay, reduced social interaction. To investigate pathophysiology of microdeletion syndromes, we generated three mouse models: 1) deletion (Del/+); 2) duplication (Dup/+) syntenic region; 3)...
Random chemical mutagenesis of the mouse genome can causally connect genes to specific phenotypes. Using this approach, reduced pinna (rep) or microtia, a defect in ear development, was mapped small region chromosome 2. Sequencing established co-segregation phenotype with mutation Prkra gene, which encodes protein PACT/RAX. Mice homozygous for mutant allele had defects not only development but also growth, craniofacial and ovarian structure. The rep identified as missense (Serine 130...
Partial monosomy 21 (PM21) is a rare chromosomal abnormality that characterized by the loss of variable segment along human chromosome (Hsa21). The clinical phenotypes this are heterogeneous and range from mild alterations to lethal consequences, depending on affected region Hsa21. most common features include intellectual disabilities, craniofacial dysmorphology, short stature, muscular cardiac defects. As complement genetic approaches, our team has developed new monosomic mouse models...
We review all recent contributions to the literature on stochastic processes. In particular, Relativistic Ornstein‐Uhlenbeck Process is presented in detail, as intrinsic Brownian motion studied by Franchi and Le Jan. The Motion of Dunkel Hänggi also reviewed, together with a model introduced Oron Horwitz. finally suggest some possible future developements current research.
ABSTRACT The most frequent and unique features of Down syndrome (DS) are learning disability ucraniofacial (CF) dysmorphism. DS-specific CF an overall reduction in head dimensions (microcephaly), relatively wide neurocranium (brachycephaly), reduced mediolaterally orbital region, bizygomatic breadth, small maxilla, mandible, increased individual variability. Until now, the cellular molecular mechanisms underlying specific craniofacial phenotype have remained poorly understood. Investigating...
Abstract Genetic factors are known to contribute Late Onset Alzheimer’s disease (LOAD) but their contribution pathophysiology, specially prodomic phases accessible therapeutic approaches far be understood. To translate genetic risk of (AD) into mechanistic insight, we generated transgenic mouse lines that express a ∼195 kbp human BAC includes only BIN1 , gene associated LOAD. This model gives modest overexpression, dependent the number copies. At 6 months age, detected impaired entorhinal...
Autism spectrum disorders affect more than 1% of the population, impairing social communication and increasing stereotyped behaviours. A micro-deletion 16p11.2 BP4-BP5 chromosomic region has been identified in patients also displaying intellectual disabilities. In mouse models generated to understand mechanisms this deletion, learning memory deficits were pervasive most genetic backgrounds, while only detected some models. To complement previous studies, we itemized model deletion on a...
The recently constructed minimal extension of the special relativistic Ornstein-Uhlenbeck process to curved space-time cannot be used model realistically diffusions on cosmological scales because it does not take into account evolution thermodynamical state matter with time. We therefore introduce a new class non-minimal extensions characterized by time-dependent friction and noise coefficients. These processes admit Jüttner distributions as possible measures in momentum space; associated...
Abstract Down syndrome (DS) is the most common genetic form of intellectual disability caused by presence an additional copy human chromosome 21 (Hsa21). To provide novel insights into genotype–phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging (MRI) and hippocampal gene expression to screen several DS mouse models for 16 region homologous Hsa21. First, unravelled interactions between different regions how they contribute significantly altering outcome...