Accepted_test

Generation of iPSCs from a Patient with the M694V Mutation in the MEFV Gene Associated with Familial Mediterranean Fever and Their Differentiation into Macrophages

by Roksana Zakharyan | Russian-Armenian University

Abstract ID: 742

Event: BGRS-abstracts

Sections: [Sym 9] Section “Gene and genome editing in modeling human pathological disease processes”

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Motivation and Aim: Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and re-current autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of vari-ous diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF.

Methods and Algorithms: In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene.

Results: As a result, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages de-rived from iPSCs of a patient with the MEFV mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type MEFV gene.

Conclusion: Such kind of cell platforms will be valuable for understanding the effects of the mutations on pyrin inflammasome dysfunction in FMF.

Funding: No. 075-15-2021-1063/10 (RF), N 21SCG-1F010 (RA), Budget project of the Institute of Cytology and Genetics (FWNR-2022-0015).