B6.129S7-Del(16Kcnj15-Mx2)13Yey/J

Stock number: 028292
Product name: Df(16)6Yey
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Df(16)6Yey/+ mutant mice have segment of mouse Chromosome 16 deleted. The sequence is defined by the Kcnj15 and Mx2 genes. These mice may have applications in studies related to understanding the developmental defects associated with Down syndrome.

Detailed description

This Df(16)6Yey/+ mutant strain has a segment of mouse Chromosome 16 deleted. The sequence is defined by the potassium inwardly-rectifying channel, subfamily J, member 15 (Kcnj15) gene and the MX dynamin-like GTPase 2 (Mx2) 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 mice are fertile. Df(16)6Yey/+ contains 16 genes orthologous to genes on Hsa21. Dp(16)1Yey/Df(16)6Yey 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)6Yey mice are similar to Df(16)6Yey/+ mice and are not improved with this model.

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 between the potassium inwardly-rectifying channel, subfamily J, member 15 (Kcnj15) gene and the MX dynamin-like GTPase 2 (Mx2) gene. The cassette placed at the proximal locus (MICER clone MHPP54c08) was targeted upstream of Kcnj15 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 MHPN178b08) was targeted downstream of the Mx2 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-Tyr^c-Brd blastocysts. The donating investigator reported that the resulting chimeric Df(16)6Yey/+ mice 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 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. While one of the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 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 C57BL/6N genetic background.

Allele

Symbol: Del(16Kcnj15-Mx2)13Yey
Name: deletion, Chr 16, Y Eugene Yu 13
MGI accession ID: MGI:5689439
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Del(16Kcnj15-Mx2)13Yey
Marker name: deletion, Chr 16, Y Eugene Yu 13
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: hromosome-engineering cassettes were inserted into mouse Chromosome 16 to bracket a span between the potassium inwardly-rectifying channel, subfamily J, member 15 (Kcnj15) gene and the MX dynamin-like GTPase 2 (Mx2) gene. The cassette placed at the proximal locus (MICER clone MHPP54c08) was targeted upstream of Kcnj15 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 MHPN178b08) was targeted downstream of the Mx2 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 Kcnj15 to Mx2, which encompasses 16 genes. FISH analysis of ES cell clones confirmed the deletions.