This gene trap mutation of the Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a) gene is located in the Down syndrome critical region. The mutation results in homozygous lethality.
Y. Eugene Yu, Roswell Park Cancer Institute
Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a) is located in the Down syndrome critical region and may be involved in cognitive development. This Dyrk1am1 gene trap allele has a
beta-geo cassette inserted into intron 4 of the Dyrk1a gene. The mutation is homozygous lethal. Heterozygous mice are viable and fertile with no obvious abnormalities.
When heterozygotes are combined with mice carrying Dp(16Lipi-Zbtb21)1Yey (or Dp(16)1), double mutant mice exhibit an improved performance in T maze and fear conditioning test as compared to Dp(16)1/+ mice alone, but performance does not reach wild-type levels. This strain may be useful for studying Down syndrome.
A gene trap vector (Sanger Institute Gene Trap Research - XQ0369) containing the reporter gene beta-geo (a fusion of B-galactosidase and neomycin phospotransferase II) was inserted into intron 4. The insertion disrupts the 321 amino acid kinase domain. The construct was electroporated into 129P2/OlaHsd derived E14TG2a.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for one generation and then maintained by crossing to (B6x129)F1 mice. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B6129SF1/J oocytes.
|Allele Name||gene trap XQ0369, Wellcome Trust Sanger Institute|
|Allele Type||Gene trapped (Reporter, Null/Knockout)|
|Gene Symbol and Name||Dyrk1a, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The beta-geo containing gene trap vector inserted in intron 4 resulting in disruption of the 321 amino acid kinase domain.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
When using the Dyrk1am1 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41838 in your Materials and Methods section.