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@PHDTHESIS{Kaschuba:14340,
      author       = {Kaschuba, Dagmar},
      title        = {{S}chrittmacherkanäle im olfaktorischen {E}pithel der
                      {M}aus},
      volume       = {4329},
      issn         = {0944-2952},
      school       = {Univ. Köln},
      type         = {Dr. (Univ.)},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {PreJuSER-14340, Juel-4329},
      series       = {Berichte des Forschungszentrums Jülich},
      pages        = {X, 138 p.},
      year         = {2010},
      note         = {Record converted from VDB: 12.11.2012; Köln, Univ., Diss.,
                      2010},
      abstract     = {HCN channels hyperpolarization-activated and
                      $\underline{c}$yclic $\underline{n}$ucleotide-gated
                      channels) are membrane proteins participating in the
                      generation of spontaneous rhythmic electrical activity in
                      cellular networks. Therefore these channels are called
                      pacemaker channels. This thesis describes for the first
                      time, the expression pattern of four different HCN channel
                      isoforms (HCN1 - HCN4) in the olfactory epithelium of the
                      mouse on a subcellular level. The isoforms HCN1 and HCN2 are
                      expressed in olfactory receptor neurons (ORN), more
                      specifically in the dendrites and axons of the ORN. Strong
                      labeling was particularly seen in the axon bundles. The HCN4
                      isoform was found almost exclusively in the axons of the
                      ORN. Furthermore, the immunohistochemical stainings allowed
                      to distinguish between two morphologically different axon
                      bundles: small, tightly-packed axon bundles which express
                      HCN 1, 2 and 4 to similar degrees, and large axon bundles in
                      which predominantly HCN4 is expressed. Notably, HCN3 seems
                      not to be expressed in the olfactory epithelium of the
                      mouse. Specific shRNA molecules can be utilized to achieve a
                      post-transcriptional downregulation of genes. To this end,
                      $\underline{r}$ecombinant
                      $\underline{a}deno-$\underline{a}$ssociated
                      $\underline{v}$iruses (rAAV) were constructed allowing the
                      gene transfer of shRNA-coding sequences. In transgenic cell
                      lines which constitutively expressed specific HCN isoforms,
                      a significant downregulation of HCN1 and HCN2 gene
                      expression was achieved after infections with rAAV_shRNA
                      constructs. Especially for HCN2, de novo protein
                      biosynthesis was impaired almost completely. In a series of
                      experiments, the transduction capability of rAAV for ORN was
                      examined in vivo by virus-mediated eGFP expression. Both,
                      ORN and supporting cells were successfully transduced by
                      rAAV of serotype 2 and 5. In transduced cells, eGFP
                      expression was very high and allowed to unequivocally
                      identify the different cell types by their morphology. In
                      summary, this thesis demonstrates that rAAV-mediated gene
                      transfer is a versatile method that can be used both, to
                      introduce genes into living organisms as well as to
                      specifically knock down gene expression by rAAV_shRNA
                      thereby supporting the ultimate goal to study a proteins’
                      function in vivo. As likely candidates, individual HCN
                      isoforms might now be targeted as their subcellular
                      expression pattern has been unraveled in the olfactory
                      epithelium of the mouse.},
      cin          = {ISB-1},
      cid          = {I:(DE-Juel1)VDB922},
      pnm          = {BioSoft: Makromolekulare Systeme und biologische
                      Informationsverarbeitung},
      pid          = {G:(DE-Juel1)FUEK505},
      typ          = {PUB:(DE-HGF)11 / PUB:(DE-HGF)3},
      url          = {https://juser.fz-juelich.de/record/14340},
}