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Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18).
Dev Dyn 2019DD

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 (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.

Authors+Show Affiliations

Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri.Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, Maryland.Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri.School of Biological Sciences, University of East Anglia, Norwich, UK.School of Biological Sciences, University of East Anglia, Norwich, UK.Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, Utah.Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri.School of Biological Sciences, University of East Anglia, Norwich, UK.Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, Maryland.Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31290205

Citation

Hagan, Andrew S., et al. "Generation and Validation of Novel Conditional Flox and Inducible Cre Alleles Targeting Fibroblast Growth Factor 18 (Fgf18)." Developmental Dynamics : an Official Publication of the American Association of Anatomists, 2019.
Hagan AS, Boylan M, Smith C, et al. Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18). Dev Dyn. 2019.
Hagan, A. S., Boylan, M., Smith, C., Perez-Santamarina, E., Kowalska, K., Hung, I. H., ... Ornitz, D. M. (2019). Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18). Developmental Dynamics : an Official Publication of the American Association of Anatomists, doi:10.1002/dvdy.85.
Hagan AS, et al. Generation and Validation of Novel Conditional Flox and Inducible Cre Alleles Targeting Fibroblast Growth Factor 18 (Fgf18). Dev Dyn. 2019 Jul 10; PubMed PMID: 31290205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation and validation of novel conditional flox and inducible Cre alleles targeting fibroblast growth factor 18 (Fgf18). AU - Hagan,Andrew S, AU - Boylan,Michael, AU - Smith,Craig, AU - Perez-Santamarina,Estela, AU - Kowalska,Karolina, AU - Hung,Irene H, AU - Lewis,Renate M, AU - Hajihosseini,Mohammad K, AU - Lewandoski,Mark, AU - Ornitz,David M, Y1 - 2019/07/10/ PY - 2019/06/06/received PY - 2019/06/24/accepted PY - 2019/7/11/pubmed PY - 2019/7/11/medline PY - 2019/7/11/entrez KW - Cre-lox recombination KW - FGF signaling KW - bone development KW - knock in mice KW - reporter gene JF - Developmental dynamics : an official publication of the American Association of Anatomists JO - Dev. Dyn. N2 - 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. SN - 1097-0177 UR - https://www.unboundmedicine.com/medline/citation/31290205/Generation_and_validation_of_novel_conditional_flox_and_inducible_Cre_alleles_targeting_fibroblast_growth_factor_18_(Fgf18) L2 - https://doi.org/10.1002/dvdy.85 DB - PRIME DP - Unbound Medicine ER -