These floxed mutant mice possess loxP sites flanking exons 5 and 6 of the Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a) gene. This strain may be useful for generating conditional mutations in applications related to a range of cellular processes including, but not limited to: lymphopoiesis, transcription, mRNA splicing, and cell proliferation. Dyrk1a is located in the Chromosome 21 Down syndrome critical region.
John D. Crispino, Northwestern University
Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a is known to phosphorylate more than 30 proteins and is involved in transcription, mRNA splicing, cell proliferation, synaptic transmission, beta-amyloid regulation, tau phosphorylation, and megakaryocytic leukemia associated with Down syndrome. Dyrk1a is located in the Chromosome 21 Down syndrome critical region.
These mice possess loxP sites flanking exons 5 and 6 of the targeted Dyrk1a gene. Exons 5 and 6 encode part of the kinase domain of the protein. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 5 and 6, and the FRT-flanked PGK-NEO cassette, deleted in the cre-expressing tissues.
When bred to a strain with Cre recombinase expression during hematopoiesis (see Stock No. 006785 and Stock No. 003802 for examples), this mutant mouse strain may be useful in studies of Cyclin D3 regulation and lymphopoiesis.
A FRT site flanked targeting vector containing PGK-Neo selection cassette was utilized in the construction of this mutant. This selection cassette and a downstream loxP site were inserted downstream of exon 6 of the targeted gene, and another loxP site was inserted upstream of exon 5. This construct was electroporated into C57BL/6N derived PRX-B6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into Albino C57BL/6 blastocysts. Heterozygotes were crossed to generate Dyrk1af/f homozygotes with a black coat color (see SNP note below).
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, John D Crispino|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Dyrk1a, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a|
|Strain of Origin||C57BL/6NTac|
|Molecular Note||The targeting construct contains a loxP site inserted upstream of exon 5 and a FRT-flanked neomycin cassette and a loxP site inserted downstream of exon 6.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Dyrk1a flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #027801 in your Materials and Methods section.