O'Connor EC et al. (2024), Advancements in the use of xenopus oocytes for ...

XB-ART-60357

Expert Opin Drug Discov 2024 Feb 01;192:173-187. doi: 10.1080/17460441.2023.2270902.

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Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery.

O'Connor EC , Kambara K , Bertrand D .

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INTRODUCTION: Introduced about 50 years ago, the model of Xenopus oocytes for the expression of recombinant proteins has gained a broad spectrum of applications. The authors herein review the benefits brought from using this model system, with a focus on modeling neurological disease mechanisms and application to drug discovery. AREAS COVERED: Using multiple examples spanning from ligand gated ion channels to transporters, this review presents, in the light of the latest publications, the benefits offered from using Xenopus oocytes. Studies range from the characterization of gene mutations to the discovery of novel treatments for disorders of the central nervous system (CNS). EXPERT OPINION: Development of new drugs targeting CNS disorders has been marked by failures in the translation from preclinical to clinical studies. As progress in genetics and molecular biology highlights large functional differences arising from a single to a few amino acid exchanges, the need for drug screening and functional testing against human proteins is increasing. The use of Xenopus oocytes to enable precise modeling and characterization of clinically relevant genetic variants constitutes a powerful model system that can be used to inform various aspects of CNS drug discovery and development.

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Species referenced: Xenopus laevis
Genes referenced: aqp4 chrna4 gabarap grin1 grin2a hcn1 kcnj10 kcnma1 kcnt1 kcnt2 slc12a6 slc1a2
GO keywords: G-protein coupled receptor activity [+]

???displayArticle.disOnts??? electroclinical syndrome [+]
???displayArticle.omims??? PARKINSON DISEASE, LATE-ONSET; PD [+]

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	Figure 1. Schematic representation of the different injection procedures and possibilities.
	Figure 2. Expression and monitoring of activity in oocytes: left panel illustrates two electrode voltage-clamp (TEVC) recordings performed to monitor the activity of voltage gated sodium channels. Currents evoked by a series of depolarizing voltage steps are superimposed in the lower left panel. Middle panel illustrates the use of a reporter channel. In this example, the GABAA α5β3γ2 receptor is used to monitor activity of a potassium chloride cotransporter KCC2. Recording the reversal potential of the GABAevoked current (ERev) permits determination of the intracellular chloride concentration (lower middle panel). Plotting ERev as a function of time reflects the progressive change in the chloride gradient. Note that each point was obtained from a single cell and that the continuous line corresponds to a fitted single exponential decay. Right panel illustrates the use of a dye to monitor the intracellular concentration of zinc. The upper image was obtained in a control cell while the lower image was obtained in a cell expressing the zinc transporter zip-8. Note that the fluorescence line that can be observed in the proximity of the membrane revealing a local increase in the zinc concentration. Intensity plots, represented in the lower right graphs as a function of the distance, clearly illustrate the difference between control and zip-8 expressing cells.
	Figure 3. Principal stages of drug research and development, highlighting where oocytes can be deployed.