129S(B6)-Del(17Abcg1-Rrp1b)5Yey/J

Stock number: 017440
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

This Df(17)4Yey/+ mutant strain contains one copy of mouse Chromosome 17 with the targeted sequence deleted between, and including, the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene and ribosomal RNA processing 1 homolog B (S. cerevisiae) (Rrp1b) gene. These mice may be useful for understanding developmental and cognitive disabilities associated with Monosomy 21.

Detailed description

This Df(17)4Yey/+ mutant strain contains one copy of mouse Chromosome 17 with the targeted sequence deleted between, and including, the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene and ribosomal RNA processing 1 homolog B (S. cerevisiae) (Rrp1b) gene. Heterozygous mice are viable and fertile. This deleted region on the mouse chromosome is one of two regions orthologous to a deleted copy of human Chromosome 21 (Hsa21) which has been implicated in developmental cognitive disabilities like Down Syndrome (DS) and Monosomy 21. Dp(17)4Yey/+ lacks 19 genes on Chromosome 17 which share conserved synteny with the distal part of human 21q22.3, and is orthologous to genes on Hsa21. These mice exhibit Monosomy 21 related phenotypic defects including impaired contextual conditioning behavior, and abnormal spatial learning. These mice may be useful for understanding developmental and cognitive disabilities associated with Monosomy 21.

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 of approximately 1.1 Mb between, and including, the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene and ribosomal RNA processing 1 homolog B (S. cerevisiae) (Rrp1b) gene. The cassette placed at the proximal locus was targeted upstream of Abcg1 and contained an agouti transgene, a 3' portion of an HPRT minigene, a loxP site and puromycin resistance gene. The cassette placed at the distal locus was targeted downstream of the Rrp1b gene and contained a neomycin resistance gene, a loxP site, a 5' portion of an HPRT minigene, and a tyrosinase minigene. 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 17 with the targeted sequence deleted (Del), were injected into C57BL/6J-Tyr^c-Brd blastocysts. The resulting chimeric males were mated to C57BL/6J females and were subsequently backcrossed to 129/SvEv mice for at least 7 generations to produce a colony of Df(17)4Yey/+ mice. Upon arrival at The Jackson Laboratory these mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation.

Allele

Symbol: Del(17Abcg1-Rrp1b)5Yey
Name: deletion, Chr 17, Y Eugene Yu 5
MGI accession ID: MGI:4818361
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Del(17Abcg1-Rrp1b)1Yey; Df(Abcg1-Rrp1b)1Yey; Del(17)1Yey; Df(17)1Yey; Del5Yey
Marker symbol: Del(17Abcg1-Rrp1b)5Yey
Marker name: deletion, Chr 17, Y Eugene Yu 5
Chromosome: 17
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: Cre mediated chromosomal rearrangement between loxP sites in regions proximal to Abcg1 and distal to Rrp1b resulted in the deletion of the genes, including Abcg1 and Rrp1b, in this approximately 1.1 Mb region that is syntenic with the proximal part of human 21q22.3.