Conditional, floxed allele of the <i>Krox20</i> gene

Taillebourg, Emmanuel; Buart, Stéphanie; Charnay, Patrick

doi:10.1002/gene.10062

Cited by 36 publications

(37 citation statements)

References 16 publications

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“…All mouse lines used in this study were maintained in a mixed C57BL/6/DBA2 background. We used the following alleles or transgenes that were genotyped as indicated in the original publications: Krox20 Soriano, 1999;Voiculescu et al, 2000;Ahn et al, 2001;Srinivas et al, 2001;Taillebourg et al, 2002;Pietri et al, 2003;Vermeren et al, 2003). All animal manipulations were performed according to French and European Union regulations.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate whether the presence of central glial components in the spinal roots is a permanent feature, we made use of a conditional mutant, Krox20 Cre/flox , that combines a floxed Krox20 allele with a knock-in of the Cre recombinase in the Krox20 locus (Voiculescu et al, 2000;Taillebourg et al, 2002). In this mutant, the Krox20 gene is expressed only very transiently.…”

Section: Nerve Roots Of Krox20 Null Mice Also Contain Central-type Mymentioning

confidence: 99%

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CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function

Coulpier¹,

Decker²,

Funalot³

et al. 2010

J. Neurosci.

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Section: Methodsmentioning

confidence: 99%

Section: Nerve Roots Of Krox20 Null Mice Also Contain Central-type Mymentioning

confidence: 99%

CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function

Coulpier¹,

Decker²,

Funalot³

et al. 2010

J. Neurosci.

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“…To investigate this issue, we have developed conditional Krox20 mutations based on a floxed allele (Taillebourg et al, 2002) and using different protocols for Cre-mediated excision, which allowed us to establish animal models that mimic CHN or CMT. In particular, clinical, immunohistochemical and ultrastructural analyses established that Krox20 inactivation in the adult sciatic nerve leads to rapid demyelination as a result of Schwann cell dedifferentiation.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Myelin Maintenance Is a Dynamic Process Requiring ConstantKrox20Expression

Decker

Desmarquet-Trin-Dinh²,

Taillebourg³

et al. 2006

J. Neurosci.

152

151

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Onset of myelination in Schwann cells is governed by several transcription factors, including Krox20/Egr2, and mutations affecting Krox20 result in various human hereditary peripheral neuropathies, including congenital hypomyelinating neuropathy (CHN) and Charcot-Marie-Tooth disease (CMT). Similar molecular information is not available on the process of myelin maintenance. We have generated conditional Krox20 mutations in the mouse that allowed us to develop models for CHN and CMT. In the latter case, specific inactivation of Krox20 in adult Schwann cells results in severe demyelination, involving rapid Schwann cell dedifferentiation and increased proliferation, followed by an attempt to remyelinate and a block at the promyelinating stage. These data establish that Krox20 is not only required for the onset of myelination but that it is also crucial for the maintenance of the myelinating state. Furthermore, myelin maintenance appears as a very dynamic process in which Krox20 may constitute a molecular switch between Schwann cell myelination and demyelination programs.

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“…1A and B. To complement these mice, called Egr2-Tg hereafter, mice lacking Egr2 from the DP stage of development onwards were generated by breeding Egr2 f/f mice, which carry flanking LoxP sites around exon 2 of the Egr2 gene [28], with CD4Cre Tg mice [27]. Supporting Information Fig.…”

mentioning

confidence: 99%

Early growth response 2 regulates the survival of thymocytes during positive selection

2009

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The early growth response (Egr) transcription factor family regulates multiple steps during T-cell development. We examine here the role played by Egr2 in positive selection. In double-positive cells, Egr2 is upregulated immediately following TCR ligation, and its expression requires both the MAPK and calcineurin signaling pathways. Inducible transgenic and knockout mice were generated to cause gain-or loss-of-function of Egr2 in double-positive cells, and had reciprocal effects; more mature single-positive cells were made when Egr2 was overexpressed, and fewer when Egr2 was absent. These defects were associated with changes in the survival of positively selected cells rather than perturbation of positive selection or immediate post-selection signaling. The survival function of Egr2 at least partly depends upon its ability to activate the cytokine-mediated survival pathway, likely through negative regulation of both the IL-7R and suppressor of cytokine signaling 1 (Socs1), the molecular switch whose downregulation normally results in restored responsiveness to cytokine signaling following selection. While gain of Egr2 caused a decrease in Socs1 mRNA, loss of Egr2 resulted in downregulation of IL-7R, upregulation of Socs1, and inhibition of Stat5 phosphorylation and IL-7-mediated survival post-selection. Therefore, expression of Egr2 following positive selection links the initial TCR signaling event to subsequent survival of signaled cells. , and Egr3 is also required for the post-b-selection proliferative burst to occur [12]. These transcription factors are also induced rapidly following ligation of the abTCR, both during thymocyte selection [15] and in mature T cells responding to antigen-MHC, where Egr1 has a role in upregulation of IL2 transcription [16], and Egr2 and Egr3 are required for induction of anergy [17,18], and regulate expression of FasL [19,20]. Through its control of self-tolerance, Egr2 has also been implicated in the development of late-onset autoimmune disease [21] and is required for the development and maturation of NKT cells [22].Upregulation of Egr proteins during positive selection is dependent upon the Ras/MAPK pathway [13]. Egr proteins are direct transcriptional targets of ternary complex factor Sap-1, which is itself a substrate of Erk and essential for positive selection [23]. In addition, Egr2 and Egr3 are regulated by calcineurin signaling, likely via NFAT [13,20,22]. Both Egr1 and Egr3 have roles in positive selection. Egr1 overexpression enhances positive selection of cells with low affinity TCR [24]. Conversely, Egr1-deficient mice have impaired positive selection [25]; although the initial TCR signal is transduced, cells stall at the DP to SP transition, resulting in a numerical decrease in CD4 and CD8 SP. Animals doubly deficient for both Egr1 and Egr3 have a similar but more marked selection phenotype, and CD8 differentiation is significantly impaired [14]. For both Egr1 and Egr3, the principal reason for the alterations in SP cell number is a change in the cells' susceptibi...

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Conditional, floxed allele of the Krox20 gene

Cited by 36 publications

References 16 publications

CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function

CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function

Peripheral Myelin Maintenance Is a Dynamic Process Requiring ConstantKrox20Expression

Early growth response 2 regulates the survival of thymocytes during positive selection

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