Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432, Chernogolovka, Moscow oblast, Russia.
School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom.
Dokl Biol Sci. 2020 Sep;494(1):260-263. doi: 10.1134/S0012496620050014. Epub 2020 Oct 20.
Multimerin-1 (Mmrn-1) is a soluble protein, also known as elastin microfibril interfacer 4 (EMILIN-4), found in platelets and in the endothelium of blood vessels. Its function and role in pathology are still not fully understood. Genetic modifications in alpha-synuclein gene (Snca) locus that mapped 160 Kb apart from Mmrn-1 in mouse genome, could weigh with regulatory elements of Mmrn-1 gene. We have studied the Mmrn-1 expression in brain cortex of three mouse lines with Snca knock-out: B6(Cg)-Snca/J, B6;129-Snca/J, and B6;129X1-Snca/J. The 35-fold increase for Mmrn-1 mRNA level have been found in B6;129X1-Snca/J mice that carry in their genome foreign sequences including bacterial gene neo and a strong promoter of a mouse phosphoglycerate kinase (Pgk1) oriented towards Mmrn-1 gene. This effect on regulatory elements of Mmrn-1 gene as a result of modifications in Snca locus should be taken into consideration when using B6;129X1-Snca/J line, that is widely applied for study of neurodegeneration mechanisms.
多聚蛋白-1(Mmrn-1)是一种可溶性蛋白,也称为弹性微纤维界面蛋白 4(EMILIN-4),存在于血小板和血管内皮中。其功能和在病理学中的作用尚不完全清楚。位于小鼠基因组中距 Mmrn-1 约 160 Kb 的α-突触核蛋白基因(Snca)位点的遗传修饰可能与 Mmrn-1 基因的调节元件有关。我们研究了三种 Snca 敲除的小鼠大脑皮层中的 Mmrn-1 表达:B6(Cg)-Snca/J、B6;129-Snca/J 和 B6;129X1-Snca/J。我们发现 B6;129X1-Snca/J 小鼠的 Mmrn-1 mRNA 水平增加了 35 倍,该小鼠的基因组中包含了外来序列,包括细菌基因 neo 和一个强烈的小鼠磷酸甘油酸激酶(Pgk1)启动子,该启动子朝向 Mmrn-1 基因。在使用广泛用于研究神经退行性机制的 B6;129X1-Snca/J 品系时,应该考虑到 Snca 基因座的修饰对 Mmrn-1 基因的调节元件的这种影响。