B6.129S7-Del(16Dyrk1a-Kcnj6)14Yey/Dp(16Lipi-Zbtb21)1Yey/J

Stock number: 028290
Product name: Dp(16)1Yey/Df(16)7Yey
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Dp(16)1Yey/Df(16)7Yey mutant mice have segment of mouse Chromosome 16 deleted. The sequence is defined by the Dyrk1a and Kcnj6 genes. These mice may have applications in studies related to understanding the developmental defects associated with Down syndrome.

Detailed description

This Dp(16)1Yey/Df(16)7Yey mutant strain contains both duplicated and deleted regions of mouse Chromosome 16. The sequence is defined by the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a (Dyrk1a) 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)7Yey/+ 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)7Yey/+ deletes only 2 genes orthologous to genes on Hsa21. Dp(16)1Yey/Df(16)7Yey 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)7Yey mice are similar to Dp(16)1Yey/+ 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 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a (Dyrk1a) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus (MICER clone MHPN85f19) was targeted upstream of Dyrk1a 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-Tyr^c-Brd blastocysts. The resulting chimeric Df(16)7Yey/+ 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. Upon arrival at The Jackson Laboratory these mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Dp(16Lipi-Zbtb21)1Yey
Name: duplication, Chr 16, Y Eugene Yu 1
MGI accession ID: MGI:3714529
Generation method: Targeted
Attributes: Inserted expressed sequence
Marker symbol: Dp(16Lipi-Zbtb21)1Yey
Marker name: duplication, Chr 16, Y Eugene Yu 1
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt^b-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).

Allele

Symbol: Del(16Dyrk1a-Kcnj6)14Yey
Name: deletion, Chr 16, Y Eugene Yu 14
MGI accession ID: MGI:5689441
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Del(16Dyrk1a-Kcnj6)14Yey
Marker name: deletion, Chr 16, Y Eugene Yu 14
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: Chromosome-engineering cassettes were inserted into mouse Chromosome 16 to bracket a span between the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a (Dyrk1a) gene and the potassium inwardly-rectifying channel, subfamily J, member 6 (Kcnj6) gene. The cassette placed at the proximal locus (MICER clone MHPN85f19) was targeted upstream of Dyrk1a 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 Dyrk1a and Kcnj6. FISH analysis of ES cell clones confirmed the deletions.