These Fgfr3 knock-out mice exhibit early mortality with skeletal defects, inner ear defects, and deafness.
David Ornitz, Washington University School of Medicine
Approximately 50% of mice that are homozygous for the Fgfr3tm1Dor targeted mutation die between birth and 21 days of age. Surviving pups may live as long as 8 months. RNAase protection analysis of adult homozygous brain tissue indicates that an abnormal transcript may be generated, but that no functional protein results. Severe skeletal defects (kyphosis, scoliosis, crooked tails, curvature and overgrowth of long bones) are evident. Inner ear defects (lack of pillar cell differentiation and tunnel of Corti formation) resulting in profound deafness are also observed.
A targeting vector containing neomycin resistance and two herpes simplex virus thymidine kinase genes was used to disrupt a region encoding the Ig-like domains II and III as well as the transmembrane domain. The construct was electroporated into 129S6/SvEv-derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
|Allele Name||targeted mutation 1, David M Ornitz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Fgfr3 -|
|Gene Symbol and Name||Fgfr3, fibroblast growth factor receptor 3|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A neomycin cassette replaced 3 kb of sequence that encodes the Ig-like domain II through the transmembrane domain. RNAase protection analysis on samples derived from homozygous mutant adult brain indicates that this allele produces an aberrant transcript. However, any translation product produced would be unable to bind ligand and is predicted not to be transported to the cell surface.|
|Mutations Made By|| |
David Ornitz, Washington University School of Medicine
This strain originated on a B6;129S6 background and has been backcrossed to C57BL/6 for at least two generations (12/01).
When using the Fgfr3- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004234 in your Materials and Methods section.
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