B6;129S7-Dp(10Prmt2-Pdxk)2Yey/J

Stock number: 013529
Product name: Dp(10)2Yey/+
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

This Dp(10)2Yey/+ mutant strain contains one copy of mouse Chromosome 10 with the targeted sequence duplicated between, and including, the protein arginine N-methyltransferase 2 (Prmt2) gene and the pyridoxal (pyridoxine, vitamin B6) kinase (Pdxk) gene. These mice may be useful for understanding developmental and cognitive disabilities associated with Down's Syndrome.

Detailed description

This Dp(10)2Yey/+ mutant strain contains one copy of mouse Chromosome 10 with the targeted sequence duplicated between, and including, the protein arginine N-methyltransferase 2 (Prmt2) gene and the pyridoxal (pyridoxine, vitamin B6) kinase (Pdxk) 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 like Down Syndrome (DS). Dp(10)2Yey/+ contains a duplication syntenic to the distal part of human 21q22.3, and carries 41 genes orthologous to genes on Hsa21. When mice carrying this duplication are bred to B6;129-Dp(16Lipi-Zfp295)1Yey/J mice (Stock No. 013530) and B6;129-Dp(17Abcg1-Rrp1b)3Yey/J mice (Stock No. 013531) to create a triple duplication model containing all three Hsa21 regions, the resulting mice exhibit DS related phenotypic defects. These defects include: 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 duplication 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 10 of 129S7/SvEvBrd-Hprt1^b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 2.3 Mb between, and including, the protein arginine N-methyltransferase 2 (Prmt2) gene and pyridoxal (pyridoxine, vitamin B6) kinase (Pdxk) loci. The cassette placed at the proximal locus was targeted upstream of Prmt2 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 was targeted downstream of the Pdxk 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, correctly targeted ES cells, containing one copy of mouse Chromosome 10 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(10)2Yey/+ 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(10Prmt2-Pdxk)2Yey
Name: duplication, Chr 10, Y Eugene Yu 2
MGI accession ID: MGI:4461400
Generation method: Targeted
Attributes: Not Applicable
Marker symbol: Dp(10Prmt2-Pdxk)2Yey
Marker name: duplication, Chr 10, Y Eugene Yu 2
Chromosome: 10
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Expressed genes: Prmt2,protein arginine N-methyltransferase 2,mouse, laboratory; Pdxk,pyridoxal (pyridoxine, vitamin B6) kinase,mouse, laboratory
Molecular note: Cre mediated chromosomal rearrangement between loxP sites in regions proximal to Prmt2 and distal to Pdxk results in duplication of the genes, including Prmt2 and Pdxk, in this approximately 2.3 Mb region that is syntenic with the distal part of human 21q22.3.