Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No targeted gene product (mRNA or protein) was detected by immunoassay or RT/PCR. Pain withdrawal threshold response of mutant mice is similar to that of wildtype mice. Mutant mice exhibit mild hyperalgesia. This mutant mouse strain represents a model that may be useful in studies of the role of dynorphin in pain, substance abuse and epilepsy.
A targeting vector containing neomycin resistance was used to disrupt exon 3, all coding region of exon 4 and 1 kb of the 3' untranslated region of exon 4. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Resulting chimeric male animals were backcrossed to wildtype C57BL/6J mice. The chimeric male animals were then mated to wildtype 129S6/SvEvTac mice to generate heterozygotes before generating homozygotes.
|Allele Name||targeted mutation 1, Ute Hochgeschwender|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Dyn-; Dyntm3Ute; Pdyn-|
|Gene Symbol and Name||Pdyn, prodynorphin|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A genomic fragment containing exon 3 and part of exon 4 was replaced with a neomycin selection cassette. The deleted sequences include all of the coding region.|
|Mutations Made By|| |
Ute Hochgeschwender, Central Michigan University
This strain originated on a B6;129 background, and has been backcrossed for 8 generations on the C57BL/6J background (01-10-02).
When using the dynorphin KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004272 in your Materials and Methods section.