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1 Cover Page The handle holds various files of this Leiden University dissertation. Author: Putten, Maaike van Title: The influence of low dystrophin levels on disease pathology in mouse models for Duchenne Muscular Dystrophy Issue Date:

2 Bibliography M. Hulsker, M. van Putten, A.M. Aartsma-Rus. A new and quick Western blot system for dystrophin detection. Manuscript in preparation M. van Putten, M. Hulsker, C. Young, V.D. Nadarajah, H. Heemskerk, L. van der Weerd, G.J.B. van Ommen, A.M. Aartsma-Rus. Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double knockout mice. Submitted M. van Putten, E.M. van der Pijl, M. Hulsker, V.D. Nadarajah, I.E. Verhaart, L. van der Weerd, A.M. Aartsma-Rus. Low dystrophin levels in heart are sufficient to delay heart failure in mdx mice. Submitted C.L. Tanganyika-de Winter, H. Heemskerk, T.G. Karnaoukh, M. van Putten, S.J. de Kimpe, J. van Deutekom and A.M. Aartsma-Rus. Long term exon skipping studies with 2 -O-methyl phosphorothioate antisense oligonucleotides in dystrophic mouse models. Molecular Therapy Nucleic Acids M. van Putten, M. Hulsker, V.D. Nadarajah, S.H. van Heiningen, E. van Huizen, M. van Iterson, P. Admiraal, T. Messemaker, J.T. den Dunnen, P.A.C. t Hoen, A.M. Aartsma-Rus. The effects of low levels of dystrophin on mouse muscle function and pathology. PLoS One M. van Putten, D. Kumar, M. Hulsker, W.M.H. Hoogaars, J.J. Plomp, A. van Opstal, M. van Iterson, P. Admiraal, G.J.B. van Ommen, P.A.C. t Hoen, A.M. Aartsma-Rus. Comparison of skeletal muscle pathology and motor function of dystrophin and utrophin deficient mouse strains. Neuromuscular Disord M. van Putten, A.M. Aartsma-Rus. Opportunities and challenges for the development of antisense treatment in neuromuscular disorders. Expert Opin Biol Ther V.D. Nadarajah, M. van Putten, A. Chaouch, P. Garrood, V. Straub, H. Lochmüller, H.B. Ginjaar, A.M. Aartsma-Rus, G.J.B. van Ommen, J.T. den Dunnen, P.A.C. 't Hoen. Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in Duchenne muscular dystrophy (DMD). Neuromuscul Disord T.J. van Dooren, H.A. van Goor, M. van Putten. Handedness and asymmetry in scale-eating cichlids: antisymmetries of different strength. Evolution M. van Putten, C. de Winter, W.M. van Roon-Mom, G.J.B. van Ommen, P.A.C. 't Hoen, A.M. Aartsma-Rus. A 3 months mild functional test regime does not affect disease parameters in young mdx mice. Neuromuscul Disord

3 Curriculum Vitae Maaike van Putten was born on January 11 th 1984 in Haarlem, the Netherlands. She attended Lyceum Sancta Maria, and obtained her HAVO degree in Subsequently, she attended Biology and Medical Laboratory Sciences at the Hogeschool Leiden, where she specialized in working with experimental animals (art.12). Her bachelor internship focussed on the role of dietary folic acid and DNA methylation in utero on vascular damage and was conducted at the department of Human Genetics of the Leiden University Medical Center under supervision of Prof.dr J.A.P. Willems van Dijk. She continued working as a research technician in the summer after graduating for her Bachelor degree in Based on her strong interest for animals, she started the Master Animal Biology at the Leiden University and conducted two internships. First, she studied the effect of daily show performances on behaviour and vocalisation of bottlenose dolphins under supervision of Dr. S. Kuczaj and Prof.dr. C. ten Cate (dept. Animal Behaviour, Leiden University) at the Marine Mammal and Cognition Laboratory of the University of Southern Mississippi (USA). Her second internship was completed under supervision of Dr. T.J.M. van Dooren at the Animal Ecology department of the Leiden University where she investigated the role of foraging behaviour on the ability of adaptation in mouth opening asymmetry in scale-eating cichlids. She graduated for her Master degree in In September 2007, she started her PhD research at the department of Human Genetics ot the Leiden University Medical Center under supervision of Prof.dr. G.J.B. van Ommen and Dr. A.M. Aartsma-Rus. The results of the work conducted are presented in this thesis. During her PhD, Maaike was a working group member of the TREAT-NMD network of excellence and the Wellstone Center. She developed standard operating procedures to unify experimental protocols used to test the effects of new treatments in animal models for DMD. With the personal financial support she received from the Bontius Fellowship, Maaike has investigated physiological parameters in mdx-xist hs and mdx-utrn -/- /Xist hs mice in the group of Prof.dr. D.J. Wells at the Royal Veterinary College in London. Currently, she continues her work as a post doctoral researcher at the department of Human Genetics of the Leiden University Medical Center. 188

4 Acknowledgements Ik heb een ontzettend leuke tijd gehad tijdens mijn promotie onderzoek en zou iedereen willen bedanken die op enige wijze heeft bijgedragen aan de totstandkoming van mijn proefschrift. Gert-Jan, bedankt voor je betrokkenheid bij mijn onderzoek, je suggesties tijdens de experimenten en je kritische kijk op mijn manuscripten. Jouw input heb ik altijd als zeer waardevol beschouwd. Annemieke, jouw inzet en enthousiasme voor het onderzoek werkten zeer inspirerend en je was mijn rots in de branding als ik het even niet meer zag zitten. Bedankt voor je vertrouwen, je begeleiding en dat je mij de mogelijkheid bood deel uit te maken van de (inter)nationale Duchenne familie. Margriet, jouw bijdrage aan dit proefschrift is enorm. Dank voor al je inzet en hulp; als er iemand gedreven is dan ben jij het wel, zowel in het lab als in de fotografie. Het was zeer plezierig om met je samen te werken en ik kijk ernaar uit om deze samenwerking voort te zetten. Ook wil ik graag mijn (oud) kamer genoten bedanken; Hans, Christa, Dwi, Emile, Laura, Pietro, Silvana, Stijn en Monica. Door jullie ben ik elke dag met veel plezier naar mijn werk gegaan. Ik heb een ontzettend leuke tijd op onze koe-kamer gehad, waar ik mij al vanaf de eerste dag op m n plek voelde. Ik kon altijd bij jullie terecht met mijn vragen en frustraties en het was fijn mijn enthousiasme over o.a. leuke resultaten met jullie te kunnen delen. Ik zal in de toekomst proberen om vaker samen met jullie lunchen in plaats van achter de computer te blijven zitten. Daarnaast wil ik ook de andere exon-skippers; Isabella, Ingrid, Marcel, Willem, Nisha en Peter- Bram bedanken voor jullie hulp met de muizen, de statistiek en elk ander gebied. Verder wil ik de rest van Lab-J en de afdeling Humane Genetica bedanken voor de hulp en gezelligheid. Het is zeer plezierig en stimulerend om in zo n hechte onderzoeksgroep en afdeling te mogen werken, waar iedereen open staat voor elkaar en bereid is elkaar te helpen. I also learned a lot from my students Tobias, Lincy, Darshan, Ella, Peter, Annemarieke, Lizette and Courtney. Thank you all for the work and dedication you put into your projects. You taught me how to be a better teacher. Naast mijn collega s heb ik ook veel gehad aan de afleiding die mijn vrienden mij boden. Voornamelijk mijn voormalige HBO-labmaatjes Karijn, Ramona en Marthe hebben mij enorm gesteund. Maar ook de gezellige avonden/weekenden met Danique, Marije, Daniëlle, Susan en mijn Jovink en Normaal moaties waren onvergetelijk. Ook wil ik graag mijn familie bedanken; Ookal ging het soms boven jullie pet en was het lastig te begrijpen wat alles inhield, jullie interesse in mijn onderzoek bleef bestaan. 189

5 In het bijzonder wil ik Oma van Putten bedanken; het is fijn om een passie voor dieren en natuur met iemand te delen die er hetzelfde over denkt. En opa en oma Rutte; dank dat jullie in mij geloofden en hebben voorgehouden dat je ergens voor moet gaan zonder ooit op te geven. Jullie toonden altijd interesse in mijn bezigheden op school. Ik weet zeker dat jullie daar boven trots op me zijn! Stef en Lana, bedankt voor alle steun die ik van jullie heb gehad; jullie waren er altijd voor mij en betekenen veel voor me. Ruud en Rini, de weg die heeft geleidt tot dit boekje had ik niet zonder jullie kunnen bewandelen. Jullie hebben aan één blik genoeg om te weten hoe ik mij voel, kennen mij door en door en sturen mij waar nodig. Dank voor al jullie steun en vertrouwen. Ze zeggen wel eens, je moet het beste voor het laatste bewaren. In mijn leven is dat Bas. Lief, ik wil je bedanken voor al je geduld, je hulp en luisterend oor en het eten dat s avonds op tafel stond koud te worden omdat ik nog even wat op het lab af moest maken. Jij hebt mij enorm gesteund in mijn werk, probeerde altijd oplossingen voor problemen te vinden, en maakte het mij mogelijk om uiteindelijk tot dit eindresultaat te komen. Ik vind het geweldig dat jij in me gelooft, ookal betekende dat bijvoorbeeld dat je me dit jaar bijna niet hebt gezien. Die onvoorwaardelijke steun houdt me op de been en ik put er veel geluk en warmte uit. Bedankt voor alles. Maaike 190

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