Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Meshalkin National Medical Research Center, Ministry of Health of the Russian Federation, 630055 Novosibirsk, Russia.
Int J Mol Sci. 2024 Jun 1;25(11):6102. doi: 10.3390/ijms25116102.
Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. 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 gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type gene.
家族性地中海热（FMF）是一种系统性自身炎症性疾病，由位于 16 号染色体（16p13.3）上的 （地中海热）基因中的遗传突变引起，该基因编码 pyrin 蛋白。尽管已经有关于 突变的现有数据，但它们对导致 FMF 中观察到的自发性和复发性自身炎症攻击的病理过程发展的具体影响机制仍不清楚。诱导多能干细胞（iPSCs）由于能够分化为包括巨噬细胞在内的任何细胞类型，被认为是研究各种疾病分子遗传机制的重要工具，而巨噬细胞有助于 FMF 的发展。在这项研究中，我们从一名携带 基因第 10 外显子中 M694V、p.（Met694Val）（c.2080A>G，rs61752717）致病性突变的 FMF 亚美尼亚患者中开发了 iPSCs。通过直接分化，获得了表达 CD14 和 CD45 表面标志物的巨噬细胞。我们发现，源自携带 突变的患者 iPSCs 的巨噬细胞的形态与源自携带野生型 基因的健康供体 iPSCs 的巨噬细胞的形态明显不同。
