This Dp(16Lipi-Zfp295)1Yey (or Dp(16)1Yey/+) mutant strain contains one copy of mouse Chromosome 16 with the targeted sequence between, and including, the lipase, member I (Lipi) gene and the zinc finger protein 295 (Zfp295) gene. These mice may be useful for understanding developmental and cognitive disabilities associated with Down's Syndrome.
Y. Eugene Yu, Roswell Park Cancer Institute
It should be noted that the phenotype of these C57BL/6J-congenic Dp(16)1Yey/+ mice could vary from that originally described on a C57BL/6J;129S7/SvEvBrd genetic background. We may modify the strain description if necessary as published results become available. The phenotype of Dp(16)1Yey/+ mice on a C57BL/6J;129S7/SvEvBrd genetic background is described below:
This Dp(16)1Yey/+ mutant strain contains one copy of mouse Chromosome 16 with the targeted sequence between, and including, the lipase, member I (Lipi) gene and the zinc finger protein 295 (Zfp295) gene. Hemizygous mice are fertile. The donating investigator recently observed that 30% of offspring die shortly after birth due to heart defects. This duplicated region on the mouse chromosome is one of three regions orthologous to an extra copy of human Chromosome 21 (Hsa21) which has been implicated in developmental cognitive disabilities associated with Down Syndrome (DS). Dp(16)1Yey/+ contains a duplication orthologous to human 21q11-q22.3 and carries 113 genes orthologous to genes on Hsa21. These mice exhibit heart defects including cleft of the mitral valve, atrial and ventricular defects, and coarctation of the aorta. Some mice also display annular pancreas and malrotation of the intestines. When mice carrying this duplication are bred to B6;129-Dp(10Prmt2-Pdxk)2Yey/J mice (Stock No. 013529) and B6;129-Dp(17Abcg1-Rrp1b)3Yey/J mice (Stock No. 013531) to create a triple duplication model containing all Hsa21 orthologous regions, the resulting mice exhibit DS related phenotypic defects. These mice display reduction in body length and weight, hydrocephaly caused by aqueductal stenosis, impaired grip strength, impaired learning, and a deficit in long-term potentiation. These mice may be useful for understanding developmental and cognitive disabilities associated with DS.
Chromosome-engineering cassettes were inserted into mouse Chromosome 16 of 129S7/SvEvBrd-Hprt1b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 22.9 Mbp between the lipase, member I (Lipi) gene and the zinc finger protein 295 (Zfp295) loci. The cassette placed at the proximal locus was targeted downstream of the Lipi gene and contained an agouti transgene, a 3' portion of an HPRT minigene, a loxP site, and a puromycin resistance gene. The cassette placed at the distal locus was targeted downstream of Zfp295 and contained a neomycin resistance gene, a loxP site, a 5' portion of an HPRT minigene, and a tyrosinase minigene. Double-targeted ES cells were subjected to transient Cre recombinase expression with subsequent selection of recombinants by using hypoxanthine aminopterin thymidine (HAT) media. Correctly targeted ES cells, containing one copy of mouse Chromosome 16 with the targeted sequence duplicated (Dp), were injected into C57BL/6J-Tyrc-Brd blastocysts. The resulting chimeric mice were mated to C57BL/6J mice. Dp(16)1Yey/+ mice were subsequently backcrossed to C57BL/6J for a total of at least three generations and then sent to The Jackson Laboratory Repository in 2011. Upon arrival, Dp(16)1Yey/+ animals were bred with C57BL/6J inbred mice (Stock No. 000664) for two or more generations to generate this C57BL/6J-congenic strain.
|Allele Name||duplication, Chr 16, Y Eugene Yu 1|
|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|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|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
Dp(16)1Yey/+ mice were bred to C57BL/6J inbred mice (Stock No. 000664) for a total of at least five generations to establish this C57BL/6J-congenic Dp(16)1Yey/+ strain. When maintaining the live congenic colony, hemizygous mice may be bred with noncarrier (wildtype) mice from the colony or with C57BL/6J inbred mice. Of note, on a C57BL/6J;129S7/SvEvBrd genetic background, the donating investigator reports that 30% of triple transgenic offspring die shortly after birth due to heart defects.
When using the Dp(16)1Yey/+ mouse strain in a publication, please cite the originating article(s) and include JAX stock #013530 in your Materials and Methods section.
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