b6b9013055f5331e001e0828e21b3edf ijms-22-09545.pdf 138c4df93adeaf448743f573124f36e32d8ecf1e ijms-22-09545.pdf fe137b41e31aca1f2c5bd09265ba17279896238fc574954cf7efc609f90ed7ef ijms-22-09545.pdf Title: Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells Subject: (1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/-), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/-), Mkk4/, Mkk7/ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7–JNK pathway has a role in adult neurogenic activity. Keywords: Cre-LoxP; MKK4; MKK7; pJNK; DCX; hippocampus Author: Rubén Darío Castro-Torres, Jordi Olloquequi, Miren Etchetto, Pablo Caruana, Luke Steele, Kyra-Mae Leighton, Jesús Ureña, Carlos Beas-Zarate, Antoni Camins, Ester Verdaguer and Carme Auladell Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Sep 2 14:10:03 2021 CEST ModDate: Thu Sep 2 14:52:29 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 28071788 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CFNGMN+VnURWPalladioL Type 1 Custom yes yes no 10 0 UHWYRS+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 RPYDIJ+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 CBSLEI+URWPalladioL-BoldItal Type 1 Custom yes yes no 24 0 KFDGZJ+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 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PFDLIE+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 592 0 PFDLJF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 598 0 PFDMJB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 601 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-07 02:41:27 CEST RepresentationInformation: ijms-22-09545.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-05 19:16:21 CEST Size: 28071788 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 814 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Characterization of Mkk4 and Mkk7 Gene Deletion and Protein Elimination in the Hippocampus of Actin-CreERT2 (Cre+/-), Mkk4 /, Mkk7/ Adult Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Genetic Ablation of Mkk4 and Mkk7 Reduces Phosphorylation of JNK in the Hippocampus Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Immature Hippocampal Neurons in Actin-CreERT2(Cre+/-), Mkk4/, Mkk7/ Mice Were Misaligned and Showed Alterations in the Dendritic Pattern Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Reduction of MKK4 and MKK7 Proteins Alters the Late Differentiation of Immature Hippocampal Neurons Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Neuronal Dendritic Pattern Is Disorganized in Actin-CreERT2(Cre+/-), Mkk4/, Mkk7/ Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: The Levels of MKK4 and MKK7 Are Not Equal in the Different Tissues Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: MKK7 Plays an Essential Role in Heart and Liver Tissues Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: The Levels of JNK Phosphorylation Were Decreased in Actin-CreERT2(Cre+/-), Mkk4/, Mkk7/ Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: The Deletion of Mkk4 and Mkk7 Gene Alters Immature Hippocampal Neurons Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Material and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Tamoxifen Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Genotype Determination in Mice and Deletion on Tissue Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Preparation of Lysates Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Immunoblot Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Immunofluorescences Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Data Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells Author: Rubén Darío Castro-Torres, Jordi Olloquequi, Miren Etchetto, Pablo Caruana, Luke Steele, Kyra-Mae Leighton, Jesús Ureña, Carlos Beas-Zarate, Antoni Camins, Ester Verdaguer and Carme Auladell Subject: (1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of Mkk4 and Mkk7 (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of Mkk4/Mkk7 in adult mice and analyze their effect in hippocampal neurogenesis. (2) Methods: To achieve this goal, Actin-CreERT2 (Cre+/-), Mkk4flox/flox, Mkk7flox/flox mice were created. The administration of tamoxifen in these 2-month-old mice induced the gene deletion (Actin-CreERT2 (Cre+/-), Mkk4/, Mkk7/ genotype), which was verified by PCR, Western blot, and immunohistochemistry techniques. (3) Results: The levels of MKK4/MKK7 at 7 and 14 days after tamoxifen administration were not eliminated totally in CNS, unlike what happens in the liver and heart. These data could be correlated with the high levels of these proteins in CNS. In the hippocampus, the deletion of Mkk4/Mkk7 induced a misalignment position of immature hippocampal neurons together with alterations in their dendritic architecture pattern and maturation process jointly to the diminution of JNK phosphorylation. (4) Conclusion: All these data supported that the MKK4/MKK7 JNK pathway has a role in adult neurogenic activity. 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