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@ARTICLE{Arnsktter:291648,
      author       = {F. Arnskötter$^*$ and P. B. G. da Silva$^*$ and M. E.
                      Schouw$^*$ and C. Lukasch$^*$ and L. Bianchini$^*$ and L.
                      Sieber$^*$ and J. Garcia-Lopez and S. T. Ahmad and Y. Li and
                      H. Lin and P. Joshi$^*$ and L. Spänig$^*$ and M. Rados$^*$
                      and M. Roiuk$^*$ and M. Sepp and M. Zuckermann$^*$ and P. A.
                      Northcott and A. Patrizi$^*$ and L. Kutscher$^*$},
      title        = {{L}oss of {E}lp1 in cerebellar granule cell progenitors
                      models ataxia phenotype of {F}amilial {D}ysautonomia.},
      journal      = {Neurobiology of disease},
      volume       = {199},
      issn         = {0969-9961},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-01472},
      pages        = {106600},
      year         = {2024},
      note         = {KFZ-ZMBH Alliance /#EA:B430#LA:B430#},
      abstract     = {Familial Dysautonomia (FD) is an autosomal recessive
                      disorder caused by a splice site mutation in the gene ELP1,
                      which disproportionally affects neurons. While classically
                      characterized by deficits in sensory and autonomic neurons,
                      neuronal defects in the central nervous system have also
                      been described. Although ELP1 expression remains high in the
                      normal developing and adult cerebellum, its role in
                      cerebellar development is unknown. To explore the role of
                      Elp1 in the cerebellum, we knocked out Elp1 in cerebellar
                      granule cell progenitors (GCPs) and examined the outcome on
                      animal behavior and cellular composition. We found that
                      GCP-specific conditional knockout of Elp1 (Elp1cKO) resulted
                      in ataxia by 8 weeks of age. Cellular characterization
                      showed that the animals had smaller cerebella with fewer
                      granule cells. This defect was already apparent as early as
                      7 days after birth, when Elp1cKO animals also had fewer
                      mitotic GCPs and shorter Purkinje dendrites. Through
                      molecular characterization, we found that loss of Elp1 was
                      associated with an increase in apoptotic cell death and cell
                      stress pathways in GCPs. Our study demonstrates the
                      importance of ELP1 in the developing cerebellum, and
                      suggests that loss of Elp1 in the GC lineage may also play a
                      role in the progressive ataxia phenotypes of FD patients.},
      keywords     = {Cerebellum (Other) / Development (Other) / ELP1 (Other) /
                      Elongator complex (Other) / Familial Dysautonomia (Other) /
                      Granule cell progenitor (Other) / Neurodevelopmental
                      disorder (Other) / ataxia (Other)},
      cin          = {B430 / B140 / B062 / A320},
      ddc          = {570},
      cid          = {I:(DE-He78)B430-20160331 / I:(DE-He78)B140-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)A320-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38996985},
      doi          = {10.1016/j.nbd.2024.106600},
      url          = {https://inrepo02.dkfz.de/record/291648},
}