Dual leucine zipper kinase is required for excitotoxicity induced neuronal degeneration

ABSTRACT: To investigate the role of DLK in the adult brain, we generated mice in which excision of the DLK allele can be temporally controlled to avoid the lethality observed at early postnatal ages in DLK null mice (Hirai et al., 2006). This was done by crossing mice with DLK exons 2-5 flanked by loxP sites (DLKlox/lox) to a Tamoxifen inducible Cre-ERT transgene driven by the CMV early enhancer/chicken beta actin (CAG) promoter that expresses high levels of Cre-ERT in brain and most peripheral tissues (Hayashi and McMahon, 2002). DLKlox/lox /Cre-ERTpos mice (referred to as DLKlox;Crepos) displayed minimal recombination of the DLK allele in the absence of Tamoxifen and survived to adulthood. To induce DLK recombination, 10-12 week old DLKlox;Crepos mice were put on a Tamoxifen diet for three weeks combined with three high dose injections of Tamoxifen, which resulted in efficient excision of DLK in most brain regions. Although the vast majority of DLK protein was eliminated in many brain regions one week after completion of Tamoxifen dosing, a small amount of DLK protein was still present, consistent with the levels of unrecombined DLK observed by PCR in each brain region. Nonetheless, this dosing regimen achieved a reduction in DLK levels that was adequate to assess the function of this kinase in the adult CNS and thus, avoid confounding developmental phenotypes. To examine what changes in gene expression resulted from Tamoxifen induced excision of DLK, we performed microarray analysis on the hippocampi of five Tamoxifen treated DLKlox;Crepos (conditional knock-outs, cKO) and five DLKlox;Creneg (WT) aged matched controls.

ORGANISM(S): Mus musculus

PROVIDER: GSE50245 | GEO | 2013/08/28

SECONDARY ACCESSION(S): PRJNA217334

REPOSITORIES: GEO