B6;129S7-Dp(17Abcg1-Rrp1b)3Yey/J

Stock number: 013531
Product name: Dp(17)3Yey/+
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

This Dp(17)3Yey/+ mutant strain contains one copy of mouse Chromosome 17 with the targeted sequence duplicated 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 Down's Syndrome.

Detailed description

This Dp(17)3Yey/+ mutant strain contains one copy of mouse Chromosome 17 with the targeted sequence duplicated 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. Hemizygous mice are viable and fertile. This duplicated region on the mouse chromosome is one of three regions orthologous to an extra copy of human Chromosome 21 (Hsa21) which has been implicated in developmental cognitive disabilities associated with Down Syndrome (DS). Dp(17)3Yey/+ contains a duplication syntenic to the proximal part of human 21q22.3, and carries 19 genes orthologous to genes on Hsa21. When mice carrying this transgene are bred to B6;129-Dp(10Prmt2-Pdxk)2Yey/J mice (Stock No. 013529) and B6;129-Dp(16Lipi-Zfp295)1Yey/J mice (Stock No. 013530) to create a triple transgenic strain containing all Hsa21 regions, the resulting mice exhibit DS related neurological defects. These mice display reduction in body length and weight, hydrocephaly caused by aqueductal stenosis, impaired grip strength, impaired learning, and a deficit in long-term potentiation. 26% of triple transgenic offspring die shortly after birth due to heart defects. These mice may be useful for understanding developmental and cognitive disabilities associated with DS.

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) loci. The cassette placed at the proximal locus was targeted upstream of Abcg1 and contained a tyrosinase minigene, a 5' portion of an HPRT minigene, a loxP site, and a neomycin resistance gene. The cassette placed at the distal locus was targeted downstream of the Rrp1b gene and contained a puromycin resistance gene, a loxP site, a 3' portion of an HPRT minigene, and an agouti transgene. 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 Chromosome 17 with the targeted sequence duplicated (Dp), were injected into C57BL/6J-Tyr^c-Brd blastocysts. The resulting chimeric mice were mated to C57BL/6J mice and were subsequently backcrossed to C57BL/6J for at least 3 generations to produce a colony of Dp(17)3Yey/+ mice. Upon arrival at The Jackson Laboratory these mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Dp(17Abcg1-Rrp1b)3Yey
Name: duplication, Chr 17, Y Eugene Yu 3
MGI accession ID: MGI:4461399
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Dp(17Abcg1-Rrp1b)3Yey
Marker name: duplication, Chr 17, Y Eugene Yu 3
Chromosome: 17
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Expressed genes: Abcg1,ATP binding cassette subfamily G member 1,mouse, laboratory; Rrp1b,ribosomal RNA processing 1 homolog B (S. cerevisiae),mouse, laboratory
Molecular note: Cre mediated chromosomal rearrangement between loxP sites in regions proximal to Abcg1 and distal to Rrp1b results in duplication 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.