Sahly Iman, Fabre Véronique, Vyas Sheela, Milet Aude, Rouzeau Jean-Denis, Hamon Michel, Lazar Monique, Tronche François
CNRS UMR7148, Molecular Genetics, Neurophysiology and Behavior, Institute of Biology, Collège de France, 11 place Marcelin Berthelot, 75231, Paris Cedex 5, France.
Mol Cell Neurosci. 2007 Sep;36(1):27-35. doi: 10.1016/j.mcn.2007.05.005. Epub 2007 Jun 12.
The 5-HT1A receptor not only plays an important role in brain physiology but it may be also implicated in the etiology of behavioral disorders such as pathological anxiety. To further define the role of 5-HT1A receptor-expressing neurons, we generated a transgenic mouse line expressing Cre recombinase in these cells. The 5-HT1A receptor open reading frame was substituted for that of Cre recombinase in a BAC containing the 5-HT1A receptor gene. In adult transgenic brain, Cre expression perfectly matched the distribution of 5-HT1A receptor mRNA. Additionally, Cre-mediated DNA recombination was restricted to neuronal populations that express the receptor, e.g., cerebral cortex, septum, hippocampus, dorsal raphe, thalamic, hypothalamic and amygdaloid nuclei, and spinal cord. Recombination occurred as early as E13 in trigeminal nerve, spinal ganglia and spinal cord. This transgenic line will allow the generation of conditional mutant mice that lack specific gene products along the serotonergic pathways and represents a unique tool for studying 5-HT1A-mediated serotonin signaling in the developing and adult brain.
5-羟色胺1A受体不仅在大脑生理学中发挥重要作用，还可能与行为障碍如病理性焦虑的病因有关。为了进一步明确表达5-羟色胺1A受体的神经元的作用，我们构建了一个在这些细胞中表达Cre重组酶的转基因小鼠品系。在含有5-羟色胺1A受体基因的细菌人工染色体（BAC）中，用Cre重组酶的开放阅读框替换了5-羟色胺1A受体的开放阅读框。在成年转基因小鼠大脑中，Cre的表达与5-羟色胺1A受体mRNA的分布完全匹配。此外，Cre介导的DNA重组仅限于表达该受体的神经元群体，如大脑皮层、隔区、海马体、中缝背核、丘脑、下丘脑和杏仁核以及脊髓。在三叉神经、脊髓神经节和脊髓中，早在胚胎第13天就发生了重组。这个转基因品系将有助于产生沿5-羟色胺能通路缺乏特定基因产物的条件性突变小鼠，是研究发育中和成年大脑中5-羟色胺1A介导的5-羟色胺信号传导的独特工具。
