Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, Paris, France.
Sci Rep. 2023 Oct 16;13(1):17563. doi: 10.1038/s41598-023-42924-2.
The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented. To map C1ql1 expression and enable the specific targeting of C1ql1-expressing cells, we generated a knockin mouse model expressing the Cre recombinase under the control of C1ql1 regulatory sequences. We characterized the capacity for Cre-driven recombination in the brain and mapped Cre expression in various neuron types using reporter mouse lines. Using an intersectional strategy with viral particle injections, we show that this mouse line can be used to target specific afferents of Purkinje cells. As C1ql1 is also expressed in other regions of the brain, as well as in other tissues such as adrenal glands and colon, our mouse model is a useful tool to target C1ql1-expressing cells in a broad variety of tissues.
C1Q 补体蛋白 C1QL1 在哺乳动物中高度保守,在包括大脑在内的各种组织中表达。这种分泌蛋白与脑特异性血管生成抑制剂 3(BAI3/ADGRB3)相互作用,控制突触的形成和维持。C1ql1 在橄榄下神经元中表达,这些神经元向小脑浦肯野细胞发出投射,但在大脑的其他部位表达较少有记录。为了绘制 C1ql1 的表达图谱并实现 C1ql1 表达细胞的特异性靶向,我们生成了一种在 C1ql1 调节序列控制下表达 Cre 重组酶的敲入小鼠模型。我们使用报告小鼠系来研究 Cre 驱动的脑内重组的能力,并绘制各种神经元类型的 Cre 表达图谱。使用病毒颗粒注射的交叉策略,我们表明该小鼠品系可用于靶向浦肯野细胞的特定传入神经。由于 C1ql1 也在大脑的其他区域以及肾上腺和结肠等其他组织中表达,因此我们的小鼠模型是在广泛的组织中靶向 C1ql1 表达细胞的有用工具。