Mice that are homozygous for the fibroblast growth factor 17 (Fgf17) targeted mutation exhibit impaired social interaction behavior. The vermis cerebellum and dorsal frontal cortex are reduced in size. This mutant mouse strain may be useful in studies of neuronal development, neocortical patterning and social interaction behavior.
David M Ornitz, Washington University School of Medicine
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities. No gene product (mRNA) is detected by in situ hybridization analysis of midbrain-hindbrain from homozygous embryos. Significant portions of the inferior colliculus and the vermis cerebellum are absent in homozygotes (2 days of age and adult). The remaining midbrain and cerebellum have normal morphology although the size of the vermis cerebellum is approximately 82% of the wildtype control. The size of the rostal-most lobe of the vermis is 1/3 of the wildtype control. The fissure separating lobe III (most rostal lobe) and lobe IV does not form completely, resulting in partially fused lobes. The dorsal frontal cortex is reduced in size with a rostral shift of sensory cortical areas. Homozygotes exhibit impaired social interaction behavior. Homozygous pups vocalize less than wildtype controls when separated from mothers. Homozygous adult males display a reduction in interaction with novel ovariectomized female as part of a social recognition test and decreased social interaction in novel environments. The Donating Investigator reports that the cre recombinase gene is expressed but is not functional. This mutant mouse strain may be useful in studies of neuronal development, neocortical patterning and social interaction behavior.
A targeting vector containing sequence encoding Cre recombinase, human beta actin polyadenylation sequence and a PGKneo cassette was used to disrupt exons 1a and 1b, which encode the signal peptide, and the translational start site. (The Donating Investigator reports that the cre recombinase gene is expressed but is not functional.) The construct was electroporated into 129S6/SvEvTac derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and maintained on a mixed B6;129 background. Upon arrival at The Jackson Laboratory the mice were crossed to B6129SF1/J (STOCK no. 101043) once to establish the colony.
|Allele Name||targeted mutation 1, David M Ornitz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Fgf17-; Fgf17neo|
|Gene Symbol and Name||Fgf17, fibroblast growth factor 17|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A contstruct, in which the translational start site and two exons encoding the signal peptide were replaced by cre and neo genes, was inserted at the endogenous locus by homologous recombination. In situ hybridization showed a lack of transcript at the midbrain-hindbrain junction in homozygous mutant mice. Expression of Cre recombinase was not reported.|
|Mutations Made By|| |
David Ornitz, Washington University School of Medicine
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6;129S-Fgf17tm1Dor/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010539 in your Materials and Methods section.