STOCK Del(17Scaf8-Pde10a)15Yey/J

Stock number: 038566
Product name: Df(17)2Yey
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Df(17)2Yey/+ mutant mice have segment of mouse Chromosome 17 deleted which is defined by the Scaf8 and Pde10a genes. These mice may have applications in studies related to understanding the developmental defects associated with Down syndrome (DS). Specifically, the deletion found in this mutant strain can be used to normalize the triplicated region on Mmu17 in Ts65Dn mice (Stock No. 001924) which is not syntenic to human chromosome 21 (Hsa21). They can be used to study the effects of free trisomies in DS as well as other human diseases such as cancers.

Detailed description

This Df(17)2Yey/+ mutant strain has a segment of mouse Chromosome 17 deleted. The sequence is defined by the SR-related CTD-associated factor 8 (Scaf8) gene and the phosphodiesterase 10A (Pde10a) gene. Df(17)2Yey/+ contains a deletion of 41 genes not syntenic to genes on human Chromosome 21 (Hsa21), which has been implicated in heart defects and cognitive deficits associated with Down Syndrome (DS). This strain can be used to normalize the triplicated region on Mmu17 in Ts65Dn mice (Stock No. 001924). Df(17)2Yey/+ hemizygous mice are fertile and have shortened tails because of the haploinsufficiency of brachyury, T-box transcription factor T (Tbxt) gene included in this region.

When these Df(17)2Yey/+ mice are bred to Ts65Dn mice, the resulting Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy, an extra free chromosome with its own centromere. These mice score significantly lower in nest building compared with the wildtype littermate controls. Males also perform significantly worse than wildtype mice in the T-maze test. Both sexes performed similarly to wildtype mice in contextual fear conditioning tests and the Morris water maze test.

Ts65Dn;Df(17)2Yey/+ mice carry triplications of a set of 103 Hsa21 gene orthologs on Mmu16 (Mir155-Zbtb21) as do Dp(16)1Yey/Df(16)8Yey mice produced by crossing Stock No. 013530 and Stock No. 038567, so there are no differences in genes or gene dosages between Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey mice. However, only Ts65Dn;Df(17)2Yey/+ mice have an extra chromosome (trisomy), making them useful for studying gene dosage-dependent and dosage-independent effects of an extra chromosome at phenotypic and molecular levels.

Development

Chromosome-engineering cassettes were inserted into mouse Chromosome 17 of 129S7/SvEvBrd-Hprt1^b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span between the SR-related CTD-associated factor 8 (Scaf8) gene and the phosphodiesterase 10A (Pde10a) gene. The cassette placed at the proximal locus (MICER clone MHPN155l15) was targeted upstream of Scaf8 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 MHPP338g19) was targeted downstream of the Pde10a 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 the targeted sequence deleted (Df) on mouse Chromosome 17 were injected into C57BL/6J-Tyr^c-Brd blastocysts. The donating investigator reported that the resulting chimeric Df(17)2Yey/+ mice were bred to Ts65Dn mice (Stock No. 001924) and the colony was maintained on a mixed genetic background containing B6Ei, C3Sn, B6, and 129S7 backgrounds. The Ts65Dn allele was removed from mice sent to The Jackson Laboratory. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Del(17Scaf8-Pde10a)15Yey
Name: deletion, chromosome 17, Y Yu 15
MGI accession ID: MGI:7509492
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Del(17Scaf8-Pde10a)2Yey; Df(17)2Yey
Marker symbol: Del(17Scaf8-Pde10a)15Yey
Marker name: deletion, chromosome 17, Y Yu
Marker synonyms: Del(17Scaf8-Pde10a)2Yey
Chromosome: 17
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: Chromosome-engineering cassettes were inserted into mouse Chromosome 17, bracketing a span between the SR-related CTD-associated factor 8 (Scaf8) gene and the phosphodiesterase 10A (Pde10a) gene. The cassette placed at the proximal locus (MICER clone MHPN155l15) was targeted upstream of Scaf8 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 MHPP338g19) was targeted downstream of the Pde10a 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.