Future projects
Our future work will focus on the cellular processes that are involved in mental ratardation and dementia and the effects on gene expression functional using genetic screens. At the same time we will search for new genes that are involved in Parkinson and Alzheimer and study the contribution of these genes in these heterogeneous disorders.

Goals
The final goal is to identify genes that are involved in common neurogenetic disorders and to study the molecular and biochemical basis of these diseases.

Selected publications
Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JWF, Breuning MH , Snijders PJLM, Rutten WPF, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P. (2001) A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nature Genet 28:213-214.

Bontekoe CJM, McIlwain KL, Nieuwenhuizen IM, Yuva-Paylor LA, Nellis A, Willemsen R, Fang Z, Kirkpatrick L, Bakker CE, McAninch R, Ching Cheng N, Merriweather M, Hoogeveen AT, Nelson DL, Paylor R , Oostra BA (2002). Knockout mouse model for Fxr2: a model for mental retardation. Hum Mol Genet 11: 487-498.

De Diego Otero Y, Severijnen L, van Cappellen G, Schrier M, Oostra BA, Willemsen R (2002). Transport of FMR1-protein via granules in neurites of PC12 cells. Mol Cell Biol 22: 8332-41.

Vaessen N, Heutink P, Houwing-Duistermaat JJ, Snijders PJLM, Rademaker T, Testers L, Batstra MR, Sandkuijl LA, van Duijn CM, Oostra BA (2002). A genome-wide search for linkage-disequilibrium with type 1 diabetes mellitus in a recent genetically isolated population from the Netherlands. Diabetes 51:856-859.

Aulchenko, Y.S., Vaessen, N., Heutink, P., Pullen, J., Snijders, P.J., Hofman, A., Sandkuijl, L.A., Houwing-Duistermaat, J.J., Edwards, M., Bennett, S., Oostra, B.A. & Van Duijn, C.M. (2003). A Genome-Wide Search for Genes Involved in Type 2 Diabetes in a Recently Genetically Isolated Population From the Netherlands. Diabetes 52: 3001-3004.

Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MCJ, Squitieri F, Ibanez P, Joosse M, van Dongen JWF, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P. (2003). Mutations in the DJ-1 gene associated with autosomal recessive early onset Parkinson. Science 299: 256-259.

Willemsen, R., Hoogeveen-Westerveld, M., Reis, S., Holstege, J., Severijnen, L., Nieuwenhuizen, I., Schrier, M., VanUnen, L., Tassone, F., Hoogeveen, A., Hagerman, P., Mientjes, E., Oostra, B. (2003). The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum Mol Genet 12: 949-959.

Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B., and Bagni, C. (2003). The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses. Cell 112: 317-327.

Mientjes EJ, Willemsen R, Kirkpatrick LL, Nieuwenhuizen IM, Hoogeveen-Westerveld M, Verweij M, Reis S, Bardoni B, Hoogeveen AT, Oostra BA, Nelson DL. (2004) Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo. Hum Mol Genet. 13:1291-1302.

Di Fonzo, A., Rohe, CF., Ferreira, J., Chien, H.F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N. Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B.A., Bonifati, V. (2005). A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet, 365: 412-415.

van 't Padje S, Engels B, Blonden L, Severijnen LA, Verheijen F, Oostra BA, Willemsen R (2005). Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 gene. Dev Genes Evol 215:198-206.

Koekkoek SK, Yamaguchi K, Milojkovic BA, Dortland BR, Ruigrok TJ, Maex R, De Graaf W, Smit AE, Vanderwerf F, Bakker CE, Willemsen R, Ikeda T, Kakizawa S, Onodera K, Nelson DL, Mientjes E, Joosten M, De Schutter E, Oostra BA, Ito M, De Zeeuw CI (2005). Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome. Neuron 47:339-352.

Reviews

Heutink P, Oostra BA (2002) Gene finding in genetically isolated populations. Hum Mol Genet 11:2507-2515.

Oostra, B. A., and Willemsen, R. (2003). A fragile balance: FMR1 expression levels. Hum Mol Genet 12: R249-257.

Willemsen R, Oostra BA, Bassell GJ, Dictenberg J. (2004) The fragile X syndrome: From molecular genetics to neurobiology. Ment Retard Dev Disabil Res Rev. 10:60-67.

Willemsen R, Mientjes E, Oostra BA (2005) FXTAS: A Progressive Neurologic Syndrome Associated with Fragile X Premutation. Curr Neurol Neurosci Rep 5:405-410