129-Dp(16Ifnar1-Kcnj6)10Yey/J

Stock number: 024908
Product name: Dp(16)4Yey/+
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Dp(16)4Yey/+ mutant mice contain a 3.7 Mb duplicated segment between the Ifnar1 and Kcnj6 genes on mouse Chromosome 16. These mice may have applications in studies related to understanding the developmental heart defects associated with Down syndrome.

Detailed description

This Dp(16)4Yey/+ mutant strain contains a duplicated segment of mouse Chromosome 16. The sequence is defined by the interferon (alpha and beta) receptor 1 (Ifnar1) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. Hemizygous mice are fertile. This duplicated region is located in one of three mouse chromosome regions orthologous to an extra copy of human Chromosome 21 (Hsa21) implicated in heart defects associated with Down Syndrome (DS). Dp(16)4Yey/+ contains 35 genes orthologous to genes on Hsa21, and thus decreases the minimal critical genomic region to 3.7 Mb on Chr 16. These mice exhibit heart defects including transposition of great arteries, atrioventricular defect, and double outlet right ventricle.

Development

Chromosome-engineering cassettes were inserted into mouse Chromosome 16 of 129S7/SvEvBrd-Hprt1^b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 3.7 Mb between the interferon (alpha and beta) receptor 1 (Ifnar1) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus was targeted upstream of Ifnar1 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 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, Double-targeted ES cells, containing one copy of mouse Chromosome 16 with the targeted sequence duplicated (Dp) on one homolog and the reciprocal deletion (Df) on the other homolog, were injected into C57BL/6J-Tyr^c-Brd blastocysts. The resulting chimeric mice were mated to 129Sv mice and the Dp(16)4Yey allele was isolated. These Dp(16)4Yey/+ mice were backcrossed to 129Sv for at least 4 generations to produce a colony. Upon arrival at The Jackson Laboratory these mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Dp(16Ifnar1-Kcnj6)10Yey
Name: duplication, Chr 16, Y Eugene Yu 10
MGI accession ID: MGI:5561090
Generation method: Targeted
Synonyms: Dp(16)10Yey; Dp(16)4Yey; Dp(16Ifnar1-Kcnj6)4Yey; Ts6Yey
Marker symbol: Dp(16Ifnar1-Kcnj6)10Yey
Marker name: duplication, Chr 16, Y Eugene Yu 10
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: This duplication was generated by recombination between two MICER clone insertions (MHPn247l16 and MHPP54c08). The 3.7 Mb duplication spans Ifnar1 to Kcnj6, which contains 17 Hsa21 gene orthologs. The duplication retains the puromycin and neomycin resistance cassettes from the original MICER clones.