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Mouse Genetic Models Core

Director

David Ornitz
Developmental Biology
314-362-3908
dornitz@wustl.edu

Associate Director

Fanxin Long
Orthopaedic Surgery
314-454-8795
longf@wudosis.wustl.edu

Mouse Model Database

Debabrata Patra
314-454-8823
patrad@wudosis.wustl.edu

Billing Administrator

Kami McGhee
Orthopaedic Surgery
314-747-5993
314-454-5900 - fax
mcgheek@wudosis.wustl.edu

Mouse line: Fgf18-CreER knockin mouse

FGF18 is a growth factor that is essential for skeletal development. Existing information suggests that Fgf18 is expressed in the perichondrium and periosteum during embryonic development and during postnatal bone growth. Fgf18 expression is also induced during skeletal fracture healing. Additional information suggests that Fgf18 is expressed in postnatal articular chondrocytes.

Tools to conditionally target the endosteum, periosteum, and articular surface in postnatal mice would be useful to understand the function of many genes that are thought to function in these tissues. To establish new and potentially better tools for musculoskeletal research, we have designed a mouse line in which we have inserted a splice acceptor (SA), driving a GFP:CreERT2 fusion gene into an intron in the Fgf18 gene (Figure 1). This vector was designed to allow GFP:CreERT2 expression in endogenous Fgf18 expression domains in the perichondrium, periosteum, endosteum, and articular surface.

Core D has successfully generated a knockin mouse line with the SA-GFP:CreERT2 insertion (Fgf18-CreER). Initial functional testing involved mating the Fgf18-CreER allele to a Cre-dependent reporter, such as ROSA26-Lox-Stop-Lox (LSL)-tdTomato allele. In the presence of tamoxifen, which activates the CreER fusion protein, the LSL cassette is deleted, allowing tdTomato expression driven by the ubiquitous ROSA26 promoter and inserted chicken beta-actin enhancer. Cre activation in this context can thus be used to trace the lineage of cells that express the Fgf18-CreER gene at the time of tamoxifen administration. The images in Figure 2 demonstrate that tamoxifen administration to postnatal day 3-7 mice efficiently marks the lineage of endosteal, periosteal, and articular surface cells. The GFP part of the GFP:CreER fusion protein is not expressed at high enough levels to visualize in these sections at this time point. Further experiments are underway to examine expression and function of the Fgf18-CreER gene at other developmental and postnatal time points.

Through core D, we are now making this allele available to the Washington University musculoskeletal research community. If you are interested in using this mouse please contact David Ornitz.

 


Citing the grant in publications:


“Washington University Musculoskeletal Research Center (NIH P30 AR057235)”