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Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18)

  1. Author:
    Hagan, Andrew S
    Boylan,Michael
    Smith, Craig
    Perez-Santamarina, Estela
    Kowalska, Karolina
    Hung, Irene H
    Lewis, Renate M
    Hajihosseini, Mohammad K
    Lewandoski,Mark
    Ornitz, David M [ORCID]
  2. Author Address

    Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO, USA., Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., School of Biological Sciences, University of East Anglia, Norwich, UK., Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, UT, USA., Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.,
    1. Year: 2019
    2. Date: JUL 22
    3. Epub Date: 2019 07 10
  1. Journal: Developmental dynamics : an official publication of the American Association of Anatomists
  2. Type of Article: Article
  3. ISSN: 1058-8388
  1. Abstract:

    BACKGROUND: Fibroblast Growth Factor 18 (FGF18) functions in the development of several tissues, including the lung, limb bud, palate, skeleton, central nervous system, and hair follicle. Mice containing a germline knockout of Fgf18 (Fgf18-/- ) die shortly after birth. Postnatally, FGF18 is being evaluated for pathogenic roles in fibrosis and several types of cancer. The specific cell types that express FGF18 have been difficult to identify, and the function of FGF18 in postnatal development and tissue homeostasis has been hampered by the perinatal lethality of Fgf18 null mice. RESULTS: We engineered a floxed allele of Fgf18 (Fgf18flox ) that allows conditional gene inactivation and a CreERT2 knockin allele (Fgf18CreERT2 ) that allows the precise identification of cells that express Fgf18 and their lineage. We validated the Fgf18flox allele by targeting it in mesenchymal tissue and primary mesoderm during embryonic development, resulting in similar phenotypes to those observed in Fgf18 null mice. We also use the Fgf18CreERT2 allele, in combination with a conditional fluorescent reporter to confirm known and identify new sites of Fgf18 expression. CONCLUSION: These alleles will be useful to investigate FGF18 function during organogenesis and tissue homeostasis, and to target specific cell lineages at embryonic and postnatal time points. This article is protected by copyright. All rights reserved.

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External Sources

  1. DOI: 10.1002/dvdy.85
  2. PMID: 31290205
  3. WOS: 000477355300001

Library Notes

  1. Fiscal Year: FY2018-2019
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