Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/67084
Title: The application of Xenopus laevis oocytes expression system to investigate the mechanisms underlying intellectual disability in a patient carrying A Kv7.3 mutation
Authors: Schembri, Amber
Keywords: Intellectual disability
Xenopus laevis
Potassium channels
Issue Date: 2020
Citation: Schembri, A. (2020). The application of Xenopus laevis oocytes expression system to investigate the mechanisms underlying intellectual disability in a patient carrying A Kv7.3 mutation (Bachelor's dissertation).
Abstract: Mutations in Kv7 channels have been associated with several neuronal and behavioural diseases in literature, such as benign familial neonatal seizures (BFNS), epilepsy, obsessive-compulsive disorder (OCD), schizophrenia and intellectual disability. This thesis will focus on a nonsense mutation in the gene KCNQ3 which led to a deletion in the C-terminal of the voltage-gated potassium channel, Kv7.3. Kv7.3 channels produce an M-current which stabilizes the resting membrane potential, including several other roles which will be discussed in detail throughout the literature review. The C-terminal is an essential component of the channel structure it acts as a binding site for several cofactors, which aid the channel dock and anchor onto the plasma membrane, as well as be targeted by kinases and act accordingly within a signalling pathway. In this study, Xenopus laevis oocytes were injected with mRNA coding for hKv7.2WT, hKv7.3WT, hKv7.3C1347DEL homomers, hKv7.2+7.3WT, hKv7.2+7.3C1347DEL heteromers, which was transcribed from linearized pXOON plasmids carrying the wildtype KCNQ2, KCNQ3 and mutated KCNQ3 genes. The current amplitude of the injected oocytes was measured using the two-electrode voltage clamp (TEVC) electrophysiological tecnique, and depicted onto appropriate graphs. The current amplitude of the channels was also tested in response to the channel blocker tetraethylammonium (TEA) and the pore-opener Retigabine. The findings implicate C1347DEL is a loss-of-function mutation, and the channel cannot be revived by Retigabine. Application of TEA to oocytes co-injected with Kv7.2+Kv7.3 subunits also revealed a 1:1 ratio hetero-polymerization of channels.
Description: B.SC.MEDICAL BIOCHEMISTRY
URI: https://www.um.edu.mt/library/oar/handle/123456789/67084
Appears in Collections:Dissertations - FacM&S - 2020
Dissertations - FacM&SPB - 2020

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