Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells

Leone, Dino P.; Genoud, Stéphane; Atanasoski, Suzana; Grausenburger, Reinhard; Berger, Philipp; Metzger, Daniel; Macklin, Wendy B.; Chambon, Pierre; Suter, Ueli

doi:10.1016/s1044-7431(03)00029-0

Cited by 250 publications

(311 citation statements)

References 41 publications

Supporting

Mentioning

297

Contrasting

Order By: Relevance

“…1,compare N,. Combined with the pharmacokinetic data above, these data suggest that tamoxifen-dependent nuclear translocation of Cre and reporter gene induction are likely to occur within the first 12-24 h after OHT treatment, in agreement with results obtained in another tamoxifen inducible line (Leone et al, 2003). After this period, no further Cre recombination is likely to occur, but reporter genes remain constitutively expressed in targeted cells and their progeny.…”

Section: Generation Of Transgenic Mice With Inducible Cre-ert2 Under supporting

confidence: 88%

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

et al. 2006

View full text Add to dashboard Cite

To identify the fates that astroglial cells can attain in the postnatal brain, we generated mice carrying an inducible Cre recombinase (Cre-ER T2 ) controlled by the human GFAP promoter (hGFAP). In mice carrying the GCE (hGFAP-Cre-ER T2 ) transgene, OHT (4-hydroxytamoxifen) injections induced Cre recombination in astroglial cells at postnatal day 5 and allowed us to permanently tag these cells with reporter genes. Three days after recombination, reporter-tagged cells were quiescent astroglial cells that expressed the stem cell marker LeX in the subventricular zone (SVZ) and dentate gyrus (DG). After 2-4 weeks, the tagged GFAP lineage included proliferating progenitors expressing the neuronal marker Dcx (Doublecortin) in the SVZ and the DG. After 4 weeks, the GFAP lineage generated mature neurons in the olfactory bulb (OB), DG, and, strikingly, also in the cerebral cortex. A major portion of all neurons in the DG and OB born at the end of the first postnatal week were generated from GFAP ϩ cells. In addition to neurons, mature oligodendrocytes and astrocytes populating the cerebral cortex and white matter were also the progeny of GFAP ϩ astroglial ancestors. Thus, genetic fate mapping of postnatal GFAP ϩ cells reveals that they seed the postnatal brain with neural progenitors/stem cells that in turn give rise to neural precursors and their mature neuronal and oligodendrocytic progeny in many CNS regions, including the cerebral cortex.

show abstract

Section: Generation Of Transgenic Mice With Inducible Cre-ert2 Under supporting

confidence: 88%

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In these transgenic mice, Cre-mediated excision of floxed STOP cassette leads to the expression of constitutively active Mek1 and enhanced green fluorescent protein (EGFP). This results in sustained activation of ERK1/2, downstream mediators of Mek1 in the MAPK pathway, in CNP-or proteolipid protein (PLP)-expressing oligodendrocyte and Schwann cells (Gravel et al, 1998;Yuan et al, 2002;Doerflinger et al, 2003;Leone et al, 2003). Littermate mice with no Cre were used as controls, facilitating comparisons among the genotypes.…”

Section: Mouse Lines Rosa26stopflmentioning

confidence: 99%

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

et al. 2016

View full text Add to dashboard Cite

Myelin growth is a tightly regulated process driven by multiple signals. ERK1/2-MAPK signaling is an important regulator of myelin thickness. Because, in demyelinating diseases, the myelin formed during remyelination fails to achieve normal thickness, increasing ERK1/2 activity in oligodendrocytes is of obvious therapeutic potential for promoting efficient remyelination. However, other studies have suggested that increased levels of ERK1/2 activity could, in fact, have detrimental effects on myelinating cells. Because the strength, duration, or timing of ERK1/2 activation may alter the biological outcomes of cellular responses markedly, here, we investigated the effect of modulating ERK1/2 activity in myelinating cells using transgenic mouse lines in which ERK1/2 activation was upregulated conditionally in a graded manner. We found enhanced myelin gene expression and myelin growth in the adult CNS at both moderate and hyperactivated levels of ERK1/2 when upregulation commenced during developmental myelination or was induced later during adulthood in quiescent preexisting oligodendrocytes, after active myelination is largely terminated. However, a late onset of demyelination and axonal degeneration occurred at hyperelevated, but not moderately elevated, levels regardless of the timing of the upregulation. Similarly, myelin and axonal pathology occurred with elevated ERK1/2 activity in Schwann cells. We conclude that a fine tuning of ERK1/2 signaling strength is critically important for normal oligodendrocyte and Schwann cell function and that disturbance of this balance has negative consequences for myelin and axonal integrity in the long term. Therefore, therapeutic modulation of ERK1/2 activity in demyelinating disease or peripheral neuropathies must be approached with caution.

show abstract

“…(Sigma) (dissolved in a vehicle of corn oil/ethanol (10 : 1)). This tamoxifen induction protocol has previously shown superior recombination rates (Leone et al, 2003;Mori et al, 2006) and showed highly efficient recombination when used with Tg TPH2-CreERT2 mice (Weber et al, 2009). Gria1 fl/fl littermates receiving tamoxifen as above served as the control group.…”

Section: Generation Of Transgenic Gria1 5-ht à / à Micementioning

confidence: 99%

Adult AMPA GLUA1 Receptor Subunit Loss in 5-HT Neurons Results in a Specific Anxiety-Phenotype with Evidence for Dysregulation of 5-HT Neuronal Activity

Weber

Vogt

Gartside

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Both the glutamatergic and serotonergic (5-HT) systems are implicated in the modulation of mood and anxiety. Descending cortical glutamatergic neurons regulate 5-HT neuronal activity in the midbrain raphe nuclei through a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. To analyze the functional role of GLUA1-containing AMPA receptors in serotonergic neurons, we used the Cre-ERT2/loxP-system for the conditional inactivation of the GLUA1-encoding Gria1 gene selectively in 5-HT neurons of adult mice. These Gria1 5-HT À / À mice exhibited a distinct anxiety phenotype but showed no alterations in locomotion, depression-like behavior, or learning and memory. Increased anxiety-related behavior was associated with significant decreases in tryptophan hydroxylase 2 (TPH2) expression and activity, and subsequent reductions in tissue levels of 5-HT, its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine in the raphe nuclei. However, TPH2 expression and activity as well as monoamine levels were unchanged in the projection areas of 5-HT neurons. Extracellular electrophysiological recordings of 5-HT neurons revealed that, while a1-adrenoceptor-mediated excitation was unchanged, excitatory responses to AMPA were enhanced and the 5-HT 1A autoreceptor-mediated inhibitory response to 5-HT was attenuated in Gria1 5-HT À / À mice. Our data show that a loss of GLUA1 protein in 5-HT neurons enhances AMPA receptor function and leads to multiple local molecular and neurochemical changes in the raphe nuclei that dysregulate 5-HT neuronal activity and induce anxiety-like behavior.

show abstract

Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells

Cited by 250 publications

References 41 publications

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

Adult AMPA GLUA1 Receptor Subunit Loss in 5-HT Neurons Results in a Specific Anxiety-Phenotype with Evidence for Dysregulation of 5-HT Neuronal Activity

Contact Info

Product

Resources

About