129-Dp(16Tiam1-Kcnj6)6Yey/J

Stock number: 018852
Product name: Dp(16)2Yey/+
Research areas: Cardiovascular Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Dp(16)2Yey/+ mutant mice contain a duplicated segment of mouse Chromosome 16. The sequence is defined by the Tiam1 and Kcnj6 genes. These mice may have applications in studies related to understanding the developmental heart defects associated with Down syndrome.

Detailed description

This Dp(16)2Yey/+ mutant strain contains a duplicated segment of mouse Chromosome 16. The sequence is defined by the T cell lymphoma invasion and metastasis 1 (Tiam1) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. Hemizygous mice are fertile. This duplicated region is one of three regions orthologous to an extra copy of human Chromosome 21 (Hsa21) implicated in heart defects associated with Down Syndrome (DS). Dp(16)2Yey/+ contains 52 genes orthologous to genes on Hsa21. These mice exhibit heart defects including transposition of great arteries, atrioventricular defect, and double outlet right ventricle. Homozygous Dp(16)2Yey/Dp(16)2Yey mice are not viable.

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 5.43 Mb between the T cell lymphoma invasion and metastasis 1 (Tiam1) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus was targeted upstream of Tiam1 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, correctly targeted ES cells, containing one copy of mouse Chromosome 16 with the targeted sequence duplicated (Dp), were injected into C57BL/6J-Tyr^c-Brd blastocysts. The resulting chimeric mice were mated to 129Sv mice and were backcrossed to 129Sv for at least 8 generations to produce a colony of Dp(16)2Yey/+ mice. 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(16Tiam1-Kcnj6)6Yey
Name: duplication, Chr 16, Y Eugene Yu 6
MGI accession ID: MGI:5305765
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Dp(16Tiam1-Kcnj6)6Yey
Marker name: duplication, Chr 16, Y Eugene Yu 6
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: ES cells were targeted twice with MICER vectors inserting 403 kb upstream of the Tiam1 gene and 155 kb downstream of Kcnj6. Transient transfection using a cre-expression vector resulted in recombination between the two targeted sites creating a duplication/deficiency allele pair.