An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes

Glia. 2010 Jun;58(8):943-53. doi: 10.1002/glia.20976.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • Antineoplastic Agents, Hormonal / pharmacology
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bromodeoxyuridine / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Ventricles / cytology
  • Embryo, Mammalian
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / physiology*
  • Green Fluorescent Proteins / metabolism
  • Integrases / genetics
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Olfactory Bulb / cytology
  • Oligodendrocyte Transcription Factor 2
  • Proteoglycans / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Spinal Cord / cytology
  • Tamoxifen / pharmacology

Substances

  • Antigens
  • Antineoplastic Agents, Hormonal
  • Basic Helix-Loop-Helix Transcription Factors
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Proteoglycans
  • RNA, Messenger
  • chondroitin sulfate proteoglycan 4
  • Tamoxifen
  • Green Fluorescent Proteins
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Cre recombinase
  • Integrases
  • Bromodeoxyuridine