Generation of the floxed allele of the SIP1 (<i>Smad‐interacting protein 1</i>) gene for Cre‐mediated conditional knockout in the mouse

Higashi, Youichirou; Maruhashi, Mitsuji; Nelles, Luc; Putte, Tom Van de; Verschueren, Kristin; Miyoshi, Takefumi; Yoshimoto, Aki; Kondoh, Hisato; Huylebroeck, Danny

doi:10.1002/gene.10048

Cited by 101 publications

(118 citation statements)

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“…In contrast, the Sip1 RNA level was not affected by the ␦EF1 genotype (data not shown). In previous studies, no autoregulation was observed for the expression of ␦EF1 (Takagi et al, 1998) or Sip1 (Higashi et al, 2002).…”

Section: Ectopic Activation Of ␦Ef1 In Sip1 Mutant Embryosmentioning

confidence: 79%

“…To improve the efficiency of generating doublehomozygous Sip1Ϫ/Ϫ;␦EF1Ϫ/Ϫ embryos, oocyte-specific knockout of the Sip1 gene using Zp3 (zona pellucida 3)-Cre mice was carried out (Lewandoski et al, 1997). The floxed allele of the Sip1 gene used in this study was Sip1 flox(ex7) , which was described previously (Higashi et al, 2002). Sip1 flox(ex7)/ϩ ;␦EF1ϩ/Ϫ;Zp3-Cre female mice were crossed with doubleheterozygous males to obtain embryos with compound genotypes.…”

Section: Experimental Procedures Micementioning

confidence: 99%

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Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Miyoshi

Maruhashi

Putte

et al. 2006

Developmental Dynamics

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In mouse embryos, the Zfhx1 transcription factor genes, Sip1 and ␦EF1, are expressed in complementary domains in many tissues. Their possible synergism in embryogenesis was investigated by comparing the phenotype of Sip1؊/؊;␦EF1؊/؊ double homozygotes with single homozygous embryos. Unexpectedly, in Sip1؊/؊ embryos ␦EF1 was ectopically activated, suggesting a negative regulation of ␦EF1 expression by Sip1. Sip1؊/؊;␦EF1؊/؊ embryos were similar to Sip1؊/؊ embryos in short somite production and developmental arrest around E8.5, but showed more severe defects in dorsal neural tube morphogenesis accompanied by a larger reduction of Sox2 expression, ascribable to the loss of the ectopic ␦EF1 expression. Sip1؉/؊;␦EF1؊/؊ embryos develop various morphological defects after E10 that were absent in ␦EF1؊/؊ embryos even in tissues without significant overlap of Sip1 and ␦EF1 expression, and arrested during mid gestation earlier than ␦EF1؊/؊ embryos. These findings indicate that complex synergistic interactions occur between Zfhx1 transcription factor genes during mouse embryogenesis. Developmental Dynamics 235: 1941-1952, 2006.

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Section: Ectopic Activation Of ␦Ef1 In Sip1 Mutant Embryosmentioning

confidence: 79%

Section: Experimental Procedures Micementioning

confidence: 99%

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Miyoshi

Maruhashi

Putte

et al. 2006

Developmental Dynamics

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“…Mice bearing floxed alleles of Zeb2 were backcrossed to the C57BL/6 background and then to a CD4-driven cre recombinase transgenic line to induce deletion in T cells (Sawada et al, 1994;Higashi et al, 2002 deficiency did not affect the phenotype of the naive T cell compartment (not depicted). We infected WT mice and mice lacking T cell-specific expression of ZEB2 with the Armstrong strain of LCMV and monitored CD8 + T cells specific for an epitope of LCMV using MHC class I-D b tetramers loaded with the gp33 peptide (Fig.…”

Section: Impaired Responses To Infection By Zeb2-deficient Cd8 + T Cellsmentioning

confidence: 99%

“…Mice with a loxP-flanked ZEB2 allele were a gift of D. Huylebroeck (Higashi et al, 2002). These mice were originally derived on the outbred Swiss CD-1 background and were backcrossed >10 times to C57BL/6J mice to achieve 99.9% similarity, as verified by GenCheck Speed Congenics services (Harlan Laboratories, Inc.).…”

Section: Mat Erials and Met Hodsmentioning

confidence: 99%

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

Omilusik¹,

Best²,

Yu³

et al. 2015

J Cell Biol

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In response to intracellular pathogens, CD8 + T cells are activated to proliferate and differentiate into a heterogeneous population of effector T cells, which are armed to eliminate infected cells. After pathogen clearance, the majority of effector CD8 + T cells die; however, a subset survives and differentiates to long-lived memory T cells. Should reinfection occur, these memory cells undergo rapid expansion and redifferentiation into effector cells, providing superior protection compared with naive T cells and protecting the host for decades in many cases (Harty and Badovinac, 2008). The ability to selectively induce T cell memory would provide novel methods for provoking protective immunity and inform vaccine strategies.Identification of effector and memory precursor CD8 + T cells within the effector population is facilitated by their distinct expression of several surface receptors. Both subsets express high levels of CD44, whereas IL-7-receptor-α (CD127) is selectively up-regulated during the transition to long-lived memory cells (Kaech et al., 2003). Killer cell lectin-like receptor G1 (KLRG1) expression is inversely correlated with CD127 expression (Joshi et al., 2007) and identifies, in both mice and humans, a subset of terminally differentiated effector cells that possess limited proliferative potential and a shorter lifespan (Voehringer et al., 2002;Joshi et al., 2007).ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1 hi effector CD8 + T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8 + T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1 hi effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8 + T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8 + T cells. Thus, differential expression of CD127 and KLRG1 identifies two populations of T cells during the peak of an infection: KLRG1 hi CD127 lo cells that consist of shorter-lived effector and effector memory cells and KLRG1 lo CD127 hi effector cells that include the long-lived memory precursors (Kaech and Wherry, 2007;Kallies, 2008). Notably, both populations under...

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“…We deleted Sip1 using three different cre strains crossed to mice in which the critical exon 7 of Sip1 is flanked by loxP sites 19 . We used Nestin-cre to inactivate Sip1 in the entire CNS (Fig.…”

Section: Sip1 Levels Are High In Postmitotic Neocortical Cellsmentioning

confidence: 99%

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

et al. 2009

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The fate of cortical progenitors, which progressively generate neurons and glial cells during development, is determined by temporally and spatially regulated signaling mechanisms. We found that the transcription factor Sip1 (Zfhx1b), which is produced at high levels in postmitotic neocortical neurons, regulates progenitor fate non-cell autonomously. Conditional deletion of Sip1 in young neurons induced premature production of upper-layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and enhanced postnatal astrocytogenesis. The premature upper-layer generation coincided with overexpression of the neurotrophin-3 (Ntf3) gene and upregulation of fibroblast growth factor 9 (Fgf9) gene expression preceded precocious gliogenesis. Exogenous application of Fgf9 to mouse cortical slices induced excessive generation of glial precursors in the germinal zone. Our data suggest that Sip1 restrains the production of signaling factors in postmitotic neurons that feed back to progenitors to regulate the timing of cell fate switch and the number of neurons and glial cells throughout corticogenesis.

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Generation of the floxed allele of the SIP1 (Smad‐interacting protein 1) gene for Cre‐mediated conditional knockout in the mouse

Cited by 101 publications

References 11 publications

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

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Generation of the floxed allele of the SIP1 (Smad‐interacting protein 1) gene for Cre‐mediated conditional knockout in the mouse

Cited by 101 publications

References 11 publications

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

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Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection