A5067673882- Retinoids in leukemia and cellular processes
- Antioxidant Activity and Oxidative Stress
- Estrogen and related hormone effects
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Stress Responses and Cortisol
- Retinal Development and Disorders
- Biotin and Related Studies
- Click Chemistry and Applications
- Receptor Mechanisms and Signaling
- Vestibular and auditory disorders
- Vitamin C and Antioxidants Research
- Congenital heart defects research
- Adipose Tissue and Metabolism
- Memory and Neural Mechanisms
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Restless Legs Syndrome Research
- Spine and Intervertebral Disc Pathology
- Cardiovascular Function and Risk Factors
- Hearing, Cochlea, Tinnitus, Genetics
- Glaucoma and retinal disorders
Inserm
2014-2025
Institut de génétique et de biologie moléculaire et cellulaire
2016-2025
Université de Strasbourg
2016-2025
Centre National de la Recherche Scientifique
2015-2025
Fraunhofer Institute for Interfacial Engineering and Biotechnology
2024
Institut Clinique de la Souris
2006-2022
Institut de Biologie Moléculaire et Cellulaire
1998-2021
Centre National pour la Recherche Scientifique et Technique (CNRST)
2013-2021
Institut de Recherche en Sciences de la Santé
2021
Délégation Paris 5
2013
ABSTRACT We describe here the analysis of congenital malformations in compound mutant fetuses bearing null alleles one RXR (α β or γ) and RAR isotype gene. A marked synergy was observed between effects mutations RXRα RARs, as a large number developmental defects previously found mainly single mutants were recapitulated specific RXRα/RAR mutants. Several seen only type combination, whereas others several types double No either RXRβ RXRγ those any mutations. These genetic data suggest that...
We have generated mouse lines in which the RXR beta gene was disrupted by homologous recombination. Approximately 50% of homozygous mutants died before or at birth, but those that survived appeared normal except males were sterile, owing to oligo-astheno-teratozoospermia. Failure spermatid release occurred within germinal epithelium, and epididymis contained very few spermatozoa that, addition, exhibited abnormal acrosomes tails. There a progressive accumulation lipids mutant Sertoli cells,...
Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range functions, including reproductive, emotional, cognitive behaviors. We studied the contribution estrogen receptors (ERs) modulation emotional processes analyzed effects deleting ERα or ERβ mice. Behavior consistent with increased anxiety was observed principally mutant females associated reduced threshold for induction synaptic plasticity basolateral amygdala. Local increase 5-hydroxytryptamine 1a...
Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It essential that tests designed provide reliable measures process under investigation but most importantly these are reproducible across both time and laboratories. For this reason, we devised tested a set SOPs investigate behavior. Five research centers were involved France, Germany, Italy, UK in study, part EUMORPHIA program. All underwent...
Systematic behavioral phenotyping of genetically modified mice is a powerful method with which to identify the molecular factors implicated in control animal behavior, potential relevance for research into neuropsychiatric disorders. A number such disorders display sex differences, yet use female strategies has been rare practice because variability related estrous cycle. We have now investigated effects cycle battery tests C57BL/6J and BALB/cByJ inbred strains mice. Whereas performance...
Dopamine is a neuromodulator involved in the control of key physiological functions. Dopamine-dependent signal transduction activated through interaction with membrane receptors seven-transmembrane domain G protein-coupled family. Among them, dopamine D2 receptor highly expressed striatum and pituitary gland as well by mesencephalic dopaminergic neurons. Lack mice leads to locomotor parkinsonian-like phenotype tumors. The promoter has characteristics housekeeping gene. However, restricted...
The RXR gamma (RXR, retinoid X receptor) gene was disrupted in the mouse. Homozygous mutant mice developed normally and were indistinguishable from their +/- or wild-type littermates with respect to growth, fertility, viability, apparent behavior animal facility. Moreover, alpha -/-/RXR -/- beta phenotypes those of mutants, respectively. Strikingly, +/-/RXR triple mutants viable. Thus, it appears that does not exert any essential function cannot be performed by beta, one copy is sufficient...
The retinoid X receptors (RXRs) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors, thereby controlling variety (patho)-physiological processes. Although synthetic RXR ligands developed for the treatment various diseases, endogenous ligand(s) these have not been conclusively identified. We show here that mice lacking cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting compromised signaling. Using HPLC-MS and...
Fragile X syndrome (FXS) is caused by the absence of Mental Retardation Protein (FMRP) in neurons. In mouse, lack FMRP associated with an excessive translation hundreds neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation proposed to underlie observed defects glutamatergic synapse maturation and function affect preferentially mRNA species that were reported bind FMRP. How impacts synaptic which mRNAs are most important for pathology remain...
Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved this requirement, we have analyzed spatial recognition working memory mice carrying null mutations of retinoid receptors RARβ RXRγ. Double mutants appeared deficient as tested spontaneous alternation Y-maze delayed nonmatch place (DNMTP) test T-maze. These mutant did acquire, however, reference or right/left discrimination tasks T-maze...
Using genetic and pharmacological approaches, we demonstrate that both RARγ/RXRα heterodimers involved in repression events, as well PPARβ(δ)/RXRα activation are cell-autonomously required suprabasal keratinocytes for the generation of lamellar granules (LG), organelles instrumental to formation skin permeability barrier. In activating heterodimers, RXRα is transcriptionally active its AF-2 function can be inhibited by an RXR-selective antagonist. Within repressing induction transcriptional...
Abstract 9‐ cis ‐Retinoic acid was identified and claimed to be the endogenous ligand of retinoid X receptors (RXRs) in 1992. Since then, presence this compound has never been rigorously confirmed. Instead, concerns have raised by other groups that reported ‐retinoic is undetectable or its occurs at very low levels. Furthermore, these levels could not satisfactorily explain physiological activation RXR. Alternative ligands, among them various lipids, also identified, but did fulfill criteria...
An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies mice have shown moderate downregulation retinoid-mediated contributed to aging-related deficits hippocampal long-term potentiation and declarative memory (LTDM). Here, knock-out, pharmacological, nutritional approaches were used series radial-arm maze experiments with further assess...
In the dentate gyrus (DG) of mouse hippocampus, neurogenesis and astrogliogenesis persist throughout life. Adult-born neurons astrocytes originate from multipotent neural stem cells (NSCs) whose activity is tightly regulated within neurogenic niche. However, cell-intrinsic mechanisms controlling neuron-glia NSC fate choice are largely unknown. Here, we show COUP-TFI/NR2F1 expression in DG NSCs its downregulation upon neuroinflammation. By using vivo inducible knockout lines, a...
The mammalian striatum controls sensorimotor and psychoaffective functions through coordinated activities of its two striatonigral striatopallidal output pathways. Here we show that retinoic acid receptor β (RARβ) development a subpopulation GABAergic, Gad65 -positive projection neurons. In Rarb −/− knock-out mice, concomitant reduction , dopamine D1 (Drd1), substance P expression at different phases prenatal was associated with reduced number Drd1 cells birth, in contrast to normal numbers...
Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels TSH-β subunit gene expression. We have previously shown that retinoid X receptor–selective (RXR-selective) ligands can suppress TSH in vivo promoter activity vitro. The RXR-γ isotype has limited tissue distribution includes the thyrotrope cells anterior pituitary gland. In this study, we performed a detailed analysis mice lacking for isotype. These had significantly...