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@ARTICLE{Sommerkamp:179779,
      author       = {P. Sommerkamp$^*$ and A. C. Sommerkamp$^*$ and P.
                      Zeisberger$^*$ and P. L. Eiben$^*$ and A. Narr$^*$ and A.
                      Korkmaz$^*$ and A. Przybylla$^*$ and M. Sohn$^*$ and F. van
                      der Hoeven$^*$ and K. Schönig and A. Trumpp$^*$},
      title        = {{CRISPR}-{C}as9 mediated generation of a conditional
                      poly({A}) binding protein nuclear 1 ({P}abpn1) mouse model
                      reveals an essential role for hematopoietic stem cells.},
      journal      = {Scientific reports},
      volume       = {12},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2022-00886},
      pages        = {7181},
      year         = {2022},
      note         = {#EA:A010#LA:A010#},
      abstract     = {Poly(A) binding protein nuclear 1 (PABPN1) is known for its
                      role in poly(A) tail addition and regulation of poly(A) tail
                      length. In addition, it has been shown to be involved in
                      alternative polyadenylation (APA). APA is a process
                      regulating differential selection of polyadenylation sites,
                      thereby influencing protein isoform expression and 3'-UTR
                      make-up. In this study, we generated an inducible
                      Pabpn1flox/flox mouse model using crRNA-tracrRNA:Cas9
                      complexes targeting upstream and downstream genomic regions,
                      respectively, in combination with a long single-stranded DNA
                      (ssDNA) template. We performed extensive in vitro testing of
                      various guide RNAs (gRNAs) to optimize recombination
                      efficiency for in vivo application. Pabpn1flox/flox mice
                      were generated and crossed to MxCre mice for validation
                      experiments, allowing the induction of Cre expression in the
                      bone marrow (BM) by poly(I:C) (pIC) injections. Validation
                      experiments revealed successful deletion of Pabpn1 and
                      absence of PABPN1 protein. Functionally, knockout (KO) of
                      Pabpn1 led to a rapid and robust depletion of hematopoietic
                      stem and progenitor cells (HSPCs) as well as myeloid cells,
                      suggesting an essential role of Pabpn1 in the hematopoietic
                      lineage. Overall, the mouse model allows an inducible
                      in-depth in vivo analysis of the role of PABPN1 and APA
                      regulation in different tissues and disease settings.},
      cin          = {A010 / B360 / W450 / HD01},
      ddc          = {600},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)B360-20160331 /
                      I:(DE-He78)W450-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35504940},
      doi          = {10.1038/s41598-022-11203-x},
      url          = {https://inrepo02.dkfz.de/record/179779},
}