Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and, with the exception of a kinked tail, do not display any gross physical or behavioral abnormalities. Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic days 10.5 to 12.5 dpc. The gene targeting strategy introduced a stop codon in exon 3 to produce a shortened inactive gene product. No full-length wildtype gene product (protein) is detected by Southern blot analysis of homozygous embryos. By 9.5 dpc homozygous mutant embryos exhibit loss or disruption of posterior structures caudal to forelimb bud, including truncated trunk, kinked neural tube, lost or disrupted somites and lack of tailbud formation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3 by introducing a stop codon. The construct was electroporated into 129S1/Sv-p+ Tyr+ KitlSl-J/+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.
|Allele Name||targeted mutation 1, Andrew P McMahon|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Wnt-3a-; Wnt3a-; Wnt3aneo|
|Gene Symbol and Name||Wnt3a, wingless-type MMTV integration site family, member 3A|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||The insertion of neomycin selection cassette into exon 3 introduced a stop codon that results in a truncated peptide approximately one-third the normal size. Transcription of the targeted loci was detected in homozygous mutant embryos via in situ hybridization.|
|Mutations Made By|| |
Andrew McMahon, University of Southern California
The resulting chimeric male animals were crossed to C57BL/6J females. The strain is maintained as a heterozygote. The Donating Investigator reports that heterozygotes are poor breeders.
When using the Wnt3a- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004581 in your Materials and Methods section.