Arşiv ve Dokümantasyon Merkezi
Dijital Arşivi

Development and molecular analysis of CMT4B1 drosophila model

Basit öğe kaydını göster

dc.contributor Graduate Program in Molecular Biology and Genetics.
dc.contributor.advisor Battaloğlu, Esra.
dc.contributor.author Kılınç, Merve.
dc.date.accessioned 2023-03-16T11:26:15Z
dc.date.available 2023-03-16T11:26:15Z
dc.date.issued 2013.
dc.identifier.other BIO 2013 K56
dc.identifier.uri http://digitalarchive.boun.edu.tr/handle/123456789/15466
dc.description.abstract Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the peripheral nervous system. Among about 40 genes associated with the disease, MTMR2 loss-of-function mutations are classified as CMT4B1 subtype. Its protein product belongs to the myotubularins, which are phosphatases in phosphatidyl inositol metabolism. The aim of this study was to generate a Drosophila model for CMT4B1 to understand the pathogenesis of this subtype by investigating how mutant MTMR2 contributes to the disease as well as furthering the current knowledge on myotubularin proteins. Firstly, already available mutant flies with partial deletion alleles of mtm, the fly homolog for MTMR2, were analyzed in terms of neuromuscular junction (NMJ) morphology and function using immunohistochemistry and FM1-43 dye uptake assays, respectively. The boutons in the NMJs, which are the connections of motor neuron terminals to muscle cells, were studied and in the NMJs of the third instar mutant larvae, excess number of satellite boutons and subboutonic structures were observed. The immunohistochemical findings with the ubiquitous and neuronal down-regulation of mtm showed also satellite boutons. Secondly, to generate precise deletion of mtm in flies, integrase-mediated approach for gene knock-out (IMAGO) was used because the targeting vector carries attachment sites, which enable the replacement of mtm with any gene. In this study, the mtm-targeting vector was prepared by cloning the homology up- and downstream sequences of mtm into pP{white-STAR} vector. It was randomly integrated into the X chromosome even though third chromosome was targeted. The targeting construct was tried to be mobilized; however, no recombinant flies were obtained after screening the progeny and more flies should be screened to obtain mtm deficient lines. Once these flies are generated, it will be possible to knock in wild type MTMR2 and CMT-causing mutant MTMR2 in place of mtm to shed light on the molecular mechanisms leading to MTMR2-associated neurodegeneration in CMT4B1.
dc.format.extent 30 cm.
dc.publisher Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2013.
dc.subject.lcsh Neurogenetics -- Research.
dc.subject.lcsh Drosophila -- Genetics.
dc.subject.lcsh Drosophila -- Physiology.
dc.title Development and molecular analysis of CMT4B1 drosophila model
dc.format.pages xvii, 77 leaves ;


Bu öğenin dosyaları

Bu öğe aşağıdaki koleksiyon(lar)da görünmektedir.

Basit öğe kaydını göster

Dijital Arşivde Ara


Göz at

Hesabım