Research Topics
Genomes and Genes
| Rob WillemsenSummaryAffiliation: Erasmus MC Country: The Netherlands Publications
| Collaborators
|
Detail Information
Publications
The fragile X syndrome: from molecular genetics to neurobiologyRob Willemsen
CBG Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Ment Retard Dev Disabil Res Rev 10:60-7. 2004..This review highlights the role of FMRP in dendritic mRNA transport/translation in relation to synaptic plasticity, a molecular mechanism implicated in learning and memory...- FXTAS: a progressive neurologic syndrome associated with Fragile X premutationRob Willemsen
Department of Clinical Genetics, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, The Netherlands
Curr Neurol Neurosci Rep 5:405-10. 2005..This review discusses recent developments in the clinical phenotype, prevalence and screening, animal models, and molecular mechanisms of RNA-based pathogenesis in FXTAS... - Transport kinetics of FMRP containing the I304N mutation of severe fragile X syndrome in neurites of living rat PC12 cellsMariette Schrier
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Exp Neurol 189:343-53. 2004.... - Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 geneSandra van 't Padje
Department of Clinical Genetics, Erasmus MC, P O Box 1738, 3000 DR Rotterdam, The Netherlands
Dev Genes Evol 215:198-206. 2005.... 
Ultrastructural analysis of the functional domains in FMRP using primary hippocampal mouse neuronsJosien Levenga
CBG Department of Clinical Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE, P O Box 2040, Rotterdam 3000 CA, The Netherlands
Neurobiol Dis 35:241-50. 2009..In conclusion, we show that wild-type FMRP and FXR2P are able to recruit FMRP variants into RNA-granules and that the G-quartet-structure in FMR1 mRNA is not essential for its incorporation in RNA-granules...
Reduction in fragile X related 1 protein causes cardiomyopathy and muscular dystrophy in zebrafishSandra Van't Padje
CBG Department of Clinical Genetics, Erasmus MC, 3015 CE Rotterdam, The Netherlands
J Exp Biol 212:2564-70. 2009..This cardiac phenotype has not been previously described and suggests that fxr1 is essential for normal cardiac form and function...- The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansionsJavier Simon-Sanchez
Department of Clinical Genetics, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands
Brain 135:723-35. 2012..Neuropathological hallmarks include neuronal and glial inclusions, and dystrophic neurites containing transactive response DNA binding protein. Future studies are needed to explain the wide variation in clinical presentation... - The DeltaK280 mutation in MAP tau favors exon 10 skipping in vivoJohn C van Swieten
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
J Neuropathol Exp Neurol 66:17-25. 2007..These observations confirm the postulated hypothesis that the DeltaK280 mutation abolishes a splice enhancer element, which overrules the decreased microtubule binding and enhanced self-aggregation... - Prospects of TAT-mediated protein therapy for fragile X syndromeSurya A Reis
CBG-Department of Clinical Genetics, Erasmus MC, 3000 DR Rotterdam, The Netherlands
J Mol Histol 35:389-95. 2004..However, uptake efficiency and velocity was lower than expected. Neuronal uptake was highly inefficient and the fusion protein demonstrated toxicity... - Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO miceFemke M S de Vrij
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Neurobiol Dis 31:127-32. 2008..Moreover, we show for the first time a structural rescue of Fragile X related protrusion morphology with two independent mGluR5 antagonists... - The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repairSteven Bergink
MGC CBG Department of Cell Biology and Genetics, Erasmus MC, P O Box 1738, 3000DR, Rotterdam, The Netherlands
Neurobiol Dis 23:708-16. 2006..This illustrates that impairment of the ubiquitin-proteasome system (UPS) by expanded glutamine repeats, including the sequestration of HR23B, is not affecting NER... - AFQ056, a new mGluR5 antagonist for treatment of fragile X syndromeJosien Levenga
Department of Clinical Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Neurobiol Dis 42:311-7. 2011..These results suggest that AFQ056 might be a potent mGluR5 antagonist to rescue various aspects of the fragile X phenotype... - Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivoEdwin J Mientjes
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
Hum Mol Genet 13:1291-302. 2004..The results presented here point towards a role for Fxr1p in muscle mRNA transport/translation control similar to that seen for Fmrp in neuronal cells... - NPHP4 variants are associated with pleiotropic heart malformationsVanessa M French
Department of Clinical Genetics, Erasmus MC Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
Circ Res 110:1564-74. 2012..Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs... - Caldesmon is essential for cardiac morphogenesis and function: in vivo study using a zebrafish modelPing Pin Zheng
Department of Pathology, Erasmus Medical Center, JNI Room 230 c, Dr Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands
Biochem Biophys Res Commun 378:37-40. 2009..Because caldesmon expression remarkably influences cardiac muscularization, the findings are relevant for designing future therapeutic strategies in the regeneration of cardiac damage... - Transport of fragile X mental retardation protein via granules in neurites of PC12 cellsYolanda De Diego Otero
CBG Department of Clinical Genetics Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands
Mol Cell Biol 22:8332-41. 2002..This report is the first example of trafficking of RNA-containing granules with FMRP as a core constituent in living PC12 cells... - Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO miceJosien Levenga
CBG Department of Clinical Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Neurobiol Learn Mem 95:467-72. 2011..Our results show a hippocampal CA1-specific altered protrusion phenotype, which was absent in the CA3 region of the hippocampus. This suggests a subregion-specific function of FMRP in synaptic plasticity in the brain... - A fragile balance: FMR1 expression levelsBen A Oostra
Department of Clinical Genetics, Erasmus MC, The Netherlands
Hum Mol Genet 12:R249-57. 2003..The level of FMR1 mRNA is in fragile balance and is therefore critical for normal functioning... - Loss of nuclear activity of the FBXO7 protein in patients with parkinsonian-pyramidal syndrome (PARK15)Tianna Zhao
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
PLoS ONE 6:e16983. 2011..The activity of FBXO7 in the nucleus appears therefore crucial for the maintenance of brain neurons and the pathogenesis of PARK15... - CGG-repeat length and neuropathological and molecular correlates in a mouse model for fragile X-associated tremor/ataxia syndromeJudith R Brouwer
Department of Clinical Genetics, Erasmus MC Rotterdam, GE Rotterdam, The Netherlands
J Neurochem 107:1671-82. 2008..Contrary to existing hypotheses, our results suggest that inclusion formation may not depend on the elevation per se of Fmr1 transcript levels in aged CGG mice... - HeNe laser (633 nm)-coupled confocal microscope allows simulating magnetic resonance imaging/computed tomography scan of the brain and eye: a noninvasive optical approach applicable to small laboratory animalsPing Pin Zheng
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
Zebrafish 8:83-5. 2011..It represents a noninvasive imaging method with high resolution while not requiring contrast agents, enabling the detection of differential signals from normal and pathological organs such as brain and eye... - TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutationsHarro Seelaar
Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands
Brain 130:1375-85. 2007..NII are also found in some cases of familial FTD + MND without Progranulin mutations. The observation of glial TDP-43 positive inclusions in one brain is very interesting, although their pathophysiological significance is yet unknown... - FMR1: a gene with three facesBen A Oostra
Department of Clinical Genetics, Erasmus MC, P O Box 2040, 3000 CA Rotterdam, The Netherlands
Biochim Biophys Acta 1790:467-77. 2009..The presence of elevated FMR1 mRNA in FXTAS suggests that FXTAS may represent a toxic RNA gain-of-function effect. The molecular basis of POI is yet unknown. The role of the FMR1 gene in these disorders is discussed... - The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndromeRob Willemsen
CBG Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Hum Mol Genet 12:949-59. 2003..This mouse model will facilitate the possibilities to perform studies at the molecular level from onset of symptoms until the final stage of the disease... - Glut1/SLC2A1 is crucial for the development of the blood-brain barrier in vivoPing Pin Zheng
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
Ann Neurol 68:835-44. 2010..To date, there is no information on the role of Glut1 during the development of BBB. In the present study, the in vivo effects of Glut1 knockdown on the cerebral vascular development were investigated... - Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver diseaseMarialuisa Quadri
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
Am J Hum Genet 90:467-77. 2012..This work has broad implications for understanding of the manganese biology and pathophysiology in multiple human organs... - Characterization of Fxr1 in Danio rerio; a simple vertebrate model to study costamere developmentBart Engels
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
J Exp Biol 207:3329-38. 2004.... - Fragile X syndrome, the Fragile X related proteins, and animal modelsAndre T Hoogeveen
Department of Clinical Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands
Microsc Res Tech 57:148-55. 2002..Phenotypic features of the FMR1 knockout mouse, the FMR1 transgenic rescue mouse, and other novel strategies for manipulating and delivering FMRP and FXRPs to the brain and other tissues are described... - Timing of the absence of FMR1 expression in full mutation chorionic villiRob Willemsen
CBG Department of Clinical Genetics, Erasmus University, P O Box 1738, 3000 DR Rotterdam, The Netherlands
Hum Genet 110:601-5. 2002..In addition, our results indicate that the timing of both X-inactivation and full mutation FMR1 allele inactivation is different, i.e. X-inactivation occurs earlier in development than inactivation of the full mutation... - A crucial role of caldesmon in vascular development in vivoPing Pin Zheng
Department of Pathology, Erasmus Medical Center, JNI Room 230 c, Dr Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands
Cardiovasc Res 81:362-9. 2009..We explored the in vivo effects of knockdown of caldesmon on vascular development in zebrafish... - Potential therapeutic interventions for fragile X syndromeJosien Levenga
CBG Department of Clinical Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands
Trends Mol Med 16:516-27. 2010.... - Microsatellite repeat instability and neurological diseaseJudith R Brouwer
Department of Clinical Genetics, ErasmusMC, Rotterdam, The Netherlands
Bioessays 31:71-83. 2009..Finally, the question of why the often harmful unstable repeats have been maintained throughout evolution is addressed... - Cd1d-dependent regulation of bacterial colonization in the intestine of miceEdward E S Nieuwenhuis
Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Clin Invest 119:1241-50. 2009..Together, these data support a role for Cd1d in regulating intestinal colonization through mechanisms that include the control of Paneth cell function... - Dopaminergic neuronal loss and dopamine-dependent locomotor defects in fbxo7-deficient zebrafishTianna Zhao
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
PLoS ONE 7:e48911. 2012.... - Oxazolone-induced enterocolitis in zebrafish depends on the composition of the intestinal microbiotaSylvia Brugman
Laboratory of Pediatrics, Pediatric Gastroenterology, Erasmus Medical Center, Rotterdam, The Netherlands
Gastroenterology 137:1757-67.e1. 2009..Interactions between host cells and bacteria are complicated, making it a challenge to assess their relative contribution to intestinal pathology. We developed a zebrafish model of enterocolitis to study these interactions... - Haemoglobin staining for in vivo portraying of functional vasculature in experimental zebrafish embryosPing Pin Zheng
Department of Pathology, Erasmus Medical Center, Office JNI Room 230 c, Dr Molewaterplein 50, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
Biochem Biophys Res Commun 380:823-4. 2009..We conclude that Hb staining offers an informative and rapid method for in vivo portraying of functional vasculature in experimental zebrafish embryos. It is also suitable for large scale experiments... - A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's diseaseSonia M Rosso
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Ann Neurol 51:373-6. 2002..Recombinant tau protein with the S320F mutation showed a greatly reduced ability to promote microtubule assembly... - Variable phenotypic expression and extensive tau pathology in two families with the novel tau mutation L315REsther van Herpen
Department of Clinical Genetics, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Ann Neurol 54:573-81. 2003..All six tau isoforms were present in soluble brain tau. Recombinant tau proteins with the L315R mutation showed a reduced ability to promote microtubule assembly... - Knockout mouse model for Fxr2: a model for mental retardationCarola J M Bontekoe
CBG Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
Hum Mol Genet 11:487-98. 2002..The findings implicate a role for Fxr2 in central nervous system function... - Proteomic analysis of exosomes isolated from human malignant pleural effusionsMartin P Bard
Department of Pulmonary Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands
Am J Respir Cell Mol Biol 31:114-21. 2004..However, pleural fluid proteins and especially immunoglobulins are coisolated and may hamper the use of exosomes isolated from malignant effusion for immunotherapy programs... - Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritisIngrid M B H van de Laar
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
Nat Genet 43:121-6. 2011..Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis... - Dauer pheromone and G-protein signaling modulate the coordination of intraflagellar transport kinesin motor proteins in C. elegansJan Burghoorn
Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
J Cell Sci 123:2077-84. 2010..We propose a model in which GPA-3-regulated docking of kinesin-II and/or OSM-3 determines entry of IFT particles into the cilia subdomains, allowing structural and functional plasticity of cilia in response to environmental cues... - Fragile X syndrome phenotype with normal FMR1 gene studiesNigel F Clarke
Am J Med Genet A 129:326-8. 2004 - NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomesBarbara Bardoni
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, BP 10142, 67404 Illkirch, C U de Strasbourg, France
Exp Cell Res 289:95-107. 2003..These findings suggest the involvement of NUFIP1 in the export and localization of mRNA and, in association with FMRP, in the regulation of local protein synthesis near synapses... - Clinical features of boys with fragile X premutations and intermediate allelesMonica Aziz
Child Mental Health Learning Disability Service, South West London and St George s Mental Health NHS Trust, United Kingdom
Am J Med Genet B Neuropsychiatr Genet 121:119-27. 2003..Replication on larger independent samples is required to confirm our impression that fragile X premutations and intermediate alleles may be associated with important developmental disabilities and physical features... - The severe G480C cystic fibrosis mutation, when replicated in the mouse, demonstrates mistrafficking, normal survival and organ-specific bioelectricsPaul Dickinson
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Hum Mol Genet 11:243-51. 2002.... - Expression profiling suggests underexpression of the GABA(A) receptor subunit delta in the fragile X knockout mouse modelIlse Gantois
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
Neurobiol Dis 21:346-57. 2006..We consider their differential expression as provisional. It is possible that these differentially expressed genes play an important role in the cognitive and behavioral problems observed in the fragile X syndrome... - Two members of the Fxr gene family, Fmr1 and Fxr1, are differentially expressed in Xenopus tropicalisLau Blonden
CBG Dept of Clinical Genetics, Erasmus MC Rotterdam, The Netherlands
Int J Dev Biol 49:437-41. 2005..Thus, for in vivo gene function studies, this relative simple animal model may serve as a highly advantageous and complementary model... - Timing and sequence of differentiation of embryonic rat hepatocytes along the biliary epithelial lineageRobbert G E Notenboom
AMC Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Hepatology 38:683-91. 2003.... - Cognitive decline, neuromotor and behavioural disturbances in a mouse model for fragile-X-associated tremor/ataxia syndrome (FXTAS)Debby Van Dam
Laboratory of Neurochemistry and Behaviour, Institute Born Bunge, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B 2610 Wilrijk, Belgium
Behav Brain Res 162:233-9. 2005..The age-dependent cognitive decline and neuromotor disturbances may be related to the progressive cognitive and behavioural difficulties observed in FXTAS patients... - Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegansJan Burghoorn
Department of Cell Biology and Genetics, and Center for Biomedical Genetics, Erasmus Medical Center, P O Box 2040, 3000 CA Rotterdam, The Netherlands
Proc Natl Acad Sci U S A 104:7157-62. 2007..We propose that DYF-5 plays a role in the undocking of kinesin II from IFT particles and in the docking of OSM-3 onto IFT particles...