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

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 eva...

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Bibliographic Details
Published in:Developmental dynamics 2019-09, Vol.248 (9), p.882-893
Main Authors: 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.
Format: Article
Language:English
Subjects:
Alleles
Animals
bone development
Cell Lineage
Central nervous system
Cre‐lox recombination
Deactivation
Embryogenesis
Embryonic Development
Embryos
FGF signaling
Fibroblast growth factor 18
Fibroblast Growth Factors - antagonists & inhibitors
Fibroblast Growth Factors - metabolism
Fibroblast Growth Factors - physiology
Fibroblasts
Fibrosis
Flox
Fluorescence
Growth factors
Homeostasis
Integrases - genetics
knock in mice
Lethality
Limb buds
Mesenchyme
Mesoderm
Mice
Organogenesis
Palate
Phenotypes
Protein Engineering - methods
reporter gene
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Summary: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 (Fgf18 flox) that allows conditional gene inactivation and a CreERT2 knockin allele (Fgf18 CreERT2) that allows the precise identification of cells that express Fgf18 and their lineage. We validated the Fgf18 flox 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 Fgf18 CreERT2 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. Key Findings Successful generation of a floxed allele of Fgf18 and a tamoxifen inducible Cre recombinase allele driven by the Fgf18 promoter. Recapitulation of the Fgf18 null skeletal deformities by conditionally targeting Fgf18 in the mesenchyme. Identification of known and new sites of Fgf18 expression in the embryo, postnatal and juvenile skeleton, postnatal and adult visceral organs, and in the adult brain.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.85