Ornitz laboratory resources

Characterization of the biological, biochemical, developmental and
physiological activity of fibroblast growth factors (FGFs) and FGF
receptors.

Available Technology:

    * BaF3 cell lines expressing individual FGF receptors:

          FGFR1, b and c splice form

          FGFR2, b and c splice form

          FGFR3, b and c splice form

    * Expression vectors for the above mentioned FGF receptors.
    * Expression vectors for FGF9.

Expression vectors for soluble FGF receptors fused to alkaline
phosphatase (AP).

Growth factor binding assay to soluble FGF receptor-AP.

• Knockout and transgenic mice:
• Knockout mouse for FGFR3.
  Transgenic mice expressing activated FGFR3 in bone growth plates.

TG:ColII-FGFR3 (achondroplasia mutation)

TRE-FGF9 (tetracycline regulated expression of FGF9)

TRE-FGFR1* (tetracycline regulated expression of constitutive FGFR1)

Conditional Knockout mouse for FGFR2
Knockout mouse for FGF9

Knockout mouse for FGF14

Knockout mouse for FGF17

Knockout mouse for FGF18

Other FGF KOs – please inquire.

Knockout mouse for Dermo1 (AKA Twist 2) with Cre insertion: Dermo1-Cre

Conditional Cre mediated expression of p27 cell cycle inhibitor: ROSA-p27

 
Patent status:

   1. Yayon, A., Ornitz, D.M., Klagsbrun, M., Leder, P. (1993) Cells
expressing a substantial number of surface high affinity HBGF receptors but
relatively few low affinity HBGF binding sites and a system for assaying
binding to HBGF receptor. US Patent No. 5,270,197. Harvard Medical School
   2. Ornitz, D.M. (1998) Method for identifying molecules that regulate FGF
activity. U.S. Patent No. 5,733,893 and No. 5,891,655 (divisional).
Monsanto-Searle Inc.
   3. Ward, B., Ornitz, D.M., Deines, M., Bittick, T. (pending) Tracer
reagents that enhance reaction-product analysis.-Sigma Chemical Co.
   4. Ornitz, D.M. and Colvin, J.C. (2000) Animal model with disrupted Fgf9
gene. Monsanto-Searle Inc., Patent No. 6,136,040.

Investigator/Technical contact:

Dr. David Ornitz
Phone: (314) 362-3908
FAX: (314) 362-7058
Email: dornitz@wustl.edu

Technology transfer contact:

Jon Kratochvil
Technology Business Development Manager
Phone: (314) 747-0923

Email: kratochj@msnotes.wustl.edu

Technology description:

BaF3 cells are mitogenically responsive cell lines that normally required
interleukin 3 for growth. Cell lines transfected with the various forms of
the FGF receptor become mitogenically dependent on FGF.

Mice that have a homozygous null allele for FGFR3 develop skeletal abnormalities involving endochondral ossification and bone remodeling. The bones grow too long in these mice.

Transgenic mice that overexpress activated FGFR3 develop skeletal
abnormalities resembling achondroplasia in humans.

Technology application:

BaF3 cell lines can be used to quantitatively assay the activity of any
known or potentially novel FGF ligand. These cells also do not make any
heparan sulfate proteoglycan. The FGF activity on these cells requires
heparin or a molecule with related activity. These cells are therefore
useful for assaying pharmaceutical agents that effect FGF activity.
Additionally, these cells would be useful for screening any drugs that
effect FGF signaling pathways downstream of the FGF receptor.

Mouse FGFR3 knockout models may be useful to assay pharmaceuticals that
effect FGF activity directly or that effect bone development through an FGF
independent pathway. Transgenic mice that express an activated FGFR3 will be
useful to assay pharmaceuticals that can inhibit FGFR signaling pathways.

Dermo1-Cre allows tissue specific gene targeting in a variety of mesenchymal tissues including skeletal, lung, gut and perivascular.

P27 allow Cre mediated inhibition of the cell cycle.