Andrew S Hagan1, Michael Boylan2, Craig Smith1, Estela Perez-Santamarina3, Karolina Kowalska3, Irene H Hung4, Renate M Lewis5, Mohammad K Hajihosseini3, Mark Lewandoski2, David M Ornitz1. 1. Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri. 2. Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, Maryland. 3. School of Biological Sciences, University of East Anglia, Norwich, UK. 4. Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, Utah. 5. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri.
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.
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: William C Skarnes; Barry Rosen; Anthony P West; Manousos Koutsourakis; Wendy Bushell; Vivek Iyer; Alejandro O Mujica; Mark Thomas; Jennifer Harrow; Tony Cox; David Jackson; Jessica Severin; Patrick Biggs; Jun Fu; Michael Nefedov; Pieter J de Jong; A Francis Stewart; Allan Bradley Journal: Nature Date: 2011-06-15 Impact factor: 49.962
Authors: Xin Sun; Anne-Karina Perl; Rongbo Li; Sheila M Bell; Eniko Sajti; Vladimir V Kalinichenko; Tanya V Kalin; Ravi S Misra; Hitesh Deshmukh; Geremy Clair; Jennifer Kyle; Laura E Crotty Alexander; Jorge A Masso-Silva; Joseph A Kitzmiller; Kathryn A Wikenheiser-Brokamp; Gail Deutsch; Minzhe Guo; Yina Du; Michael P Morley; Michael J Valdez; Haoze V Yu; Kang Jin; Eric E Bardes; Jarod A Zepp; Terren Neithamer; Maria C Basil; William J Zacharias; Jamie Verheyden; Randee Young; Gautam Bandyopadhyay; Sara Lin; Charles Ansong; Joshua Adkins; Nathan Salomonis; Bruce J Aronow; Yan Xu; Gloria Pryhuber; Jeff Whitsett; Edward E Morrisey Journal: Dev Cell Date: 2021-12-21 Impact factor: 13.417