The Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom.
Glia. 2010 Jun;58(8):943-53. doi: 10.1002/glia.20976.
The lack of markers for astrocytes, particularly gray matter astrocytes, significantly hinders research into their development and physiological properties. We previously reported that fibroblast growth factor receptor 3 (Fgfr3) is expressed by radial precursors in the ventricular zone of the embryonic neural tube and subsequently by differentiated astrocytes in gray and white matter. Here, we describe an Fgfr3-iCreER(T2) phage artificial chromosome transgenic mouse line that allows efficient tamoxifen-induced Cre recombination in Fgfr3-expressing cells, including radial glial cells in the embryonic neural tube and both fibrous and protoplasmic astrocytes in the mature central nervous system. This mouse strain will therefore be useful for studies of normal astrocyte biology and their responses to CNS injury or disease. In addition, Fgfr3-iCreER(T2) drives Cre recombination in all neurosphere-forming stem cells in the adult spinal cord and at least 90% of those in the adult forebrain subventricular zone. We made use of this to show that there is continuous accumulation of all major interneuron subtypes in the olfactory bulb (OB) from postnatal day 50 (P50) until at least P230 ( approximately 8 months of age). It therefore seems likely that adult-born interneurons integrate into existing circuitry and perform long-term functions in the adult OB.
星形胶质细胞,尤其是灰质星形胶质细胞缺乏标志物,这极大地阻碍了对其发育和生理特性的研究。我们之前曾报道过,成纤维细胞生长因子受体 3(Fgfr3)在胚胎神经管室管膜区的放射状前体细胞中表达,随后在灰质和白质中的分化星形胶质细胞中表达。在这里,我们描述了一种 Fgfr3-iCreER(T2)噬菌体人工染色体转基因小鼠品系,该品系允许在 Fgfr3 表达细胞中进行高效的他莫昔芬诱导的 Cre 重组,包括胚胎神经管中的放射状神经胶质细胞以及成熟中枢神经系统中的纤维性和原浆性星形胶质细胞。因此,该小鼠品系将有助于研究正常星形胶质细胞生物学及其对中枢神经系统损伤或疾病的反应。此外,Fgfr3-iCreER(T2)在成年脊髓和至少 90%的成年前脑室下区的所有神经球形成干细胞中驱动 Cre 重组。我们利用这一点表明,从出生后第 50 天(P50)到至少 P230(约 8 个月大),所有主要中间神经元亚型在嗅球(OB)中持续积累。因此,似乎成年产生的中间神经元整合到现有的回路中,并在成年 OB 中执行长期功能。