Dp(16)1Yey/Df(16)5Yey mutant mice have segment of mouse Chromosome 16 deleted. The sequence is defined by the Setd4 and Kcnj6 genes. These mice may have applications in studies related to understanding the developmental defects associated with Down syndrome.
Y. Eugene Yu, Roswell Park Cancer Institute
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Inserted expressed sequence) | Dp(16Lipi-Zbtb21)1Yey | duplication, Chr 16, Y Eugene Yu 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Del(16Setd4-Kcnj6)12Yey | deletion, Chr 16, Y Eugene Yu 14 |
This Dp(16)1Yey/Df(16)5Yey mutant strain contains both duplicated and deleted regions of mouse Chromosome 16. The sequence is defined by the SET domain containing 4 (Setd4) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. This region is located in one of three mouse chromosome regions orthologous to an extra copy of human Chromosome 21 (Hsa21) implicated in heart defects and cognitive deficits associated with Down Syndrome (DS). Hemizygous Df(16)5Yey/+ mice are fertile, but produce very few mutant progeny at weaning. The inclusion of Dp(16)1Yey gene sequences increases viability of mutant offspring. Df(16)5Yey/+ contains 15 genes orthologous to genes on Hsa21. Dp(16)1Yey/Df(16)5Yey mice perform significantly worse than their wildtype littermate controls in the T-maze and contextual fear conditioning tests. After theta burst stimulation (TBS), synaptic response in brain slices are significantly lower. Learning and memory in Dp(16)1Yey/Df(16)5Yey mice are similar to Df(16)1Yey/+ mice and are not improved with this model.
Chromosome-engineering cassettes were inserted into mouse Chromosome 16 of 129S7/SvEvBrd-Hprt1b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span between the SET domain containing 4 (Setd4) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus (MICER clone MHPN267e05) was targeted upstream of Setd4 and contained a neomycin resistance gene, a loxP site, a 5' portion of an HPRT minigene, and a tyrosinase minigene. The cassette placed at the distal locus (MICER clone MHPP54c08) was targeted downstream of the Kcnj6 gene and contained an agouti transgene, a 3' portion of an HPRT minigene, a loxP site and puromycin resistance gene. Double-targeted ES cells were transiently transfected with the cre recombinase expression vector pOG231. After subsequent selection of recombinants by using hypoxanthine aminopterin thymidine (HAT) media, ES cells containing one copy of mouse Chromosome 16 with the targeted sequence deleted (Df) were injected into C57BL/6J-Tyrc-Brd blastocysts. The donating investigator reported that the resulting chimeric Df(16)5Yey/+ mice were bred to Dp(16)1Yey mice (Stock No. 013530) and then were backcrossed to C57BL/6J for 5 generations to produce a colony (see SNP note below). Upon arrival at The Jackson Laboratory these mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation.
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. Two of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross. Also, 2 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 | duplication, Chr 16, Y Eugene Yu 1 |
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Allele Type | Targeted (Inserted expressed sequence) |
Allele Synonym(s) | Dp(16)1/Yey; Dp(16)1Yey; Dp(16)1Yu; Dp(16D930038D03Tik-Zfp295)1Yey; Dp(16Lipi-Zfp295)1Yey; Dp1Yu; Ts1Yey |
Gene Symbol and Name | Dp(16Lipi-Zbtb21)1Yey, duplication, Chr 16, Y Eugene Yu 1 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 16 |
Molecular Note | A 22.9Mb region of chromosome 16 that is syntenic with human chromosome 21 was duplicated using a Cre/loxP-mediated recombination system. This region, thought to be involved in Down Syndrome, contains 113 orthologues including all markers between and including D930038D03Rik (Lipi) and Zfp295 (Zbtb21). |
Mutations Made By | Y. Eugene Yu, Roswell Park Cancer Institute |
Allele Name | deletion, Chr 16, Y Eugene Yu 12 |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Df(16)5; Df(16)5Yey |
Gene Symbol and Name | Del(16Setd4-Kcnj6)12Yey, deletion, Chr 16, Y Eugene Yu 14 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 16 |
Molecular Note | Chromosome-engineering cassettes were inserted into mouse Chromosome 16 to bracket a span between the SET domain containing 4 (Setd4) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus (MICER clone MHPN267e05) was targeted upstream of Setd4 and contained a neomycin resistance gene, a loxP site, a 5' portion of an HPRT minigene, and a tyrosinase minigene. The cassette placed at the distal locus (MICER clone MHPP54c08) was targeted downstream of the Kcnj6 gene and contained an agouti transgene, a 3' portion of an HPRT minigene, a loxP site and puromycin resistance gene. Double-targeted ES cells were transiently transfected with the cre recombinase expression vector pOG231 to remove the region from Set4 to Kcnj6, which encompasses 15 genes. FISH analysis of ES cell clones confirmed the deletions. |
When maintaining a live colony, mice must carry both Df(16)5Yey and Dp(16)1Yey gene sequences. Df(16)5Yey alone results in very few mutant progeny at weaning.
When using the Df(16)5Yey/Dp(16)1Yey mouse strain in a publication, please cite the originating article(s) and include JAX stock #028289 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterzygous or wildtype for Del(16Setd4-Kcnj6)12Ye or Heterzygous or wildtype for Dp(16Lipi-Zbtb21)1Yey |
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