129-Dp(16Tiam1-Il10rb)8Yey/J

Stock number: 024906
Product name: Dp(16)3Yey/+
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Dp(16)3Yey/+ mutant mice contain a 2.11 Mb duplicated segment between the Tiam1 and Il10rb genes on mouse Chromosome 16. These mice may have applications in studies related to understanding the developmental defects associated with Down syndrome.

Detailed description

This Dp(16)3Yey/+ mutant strain contains a 2.11 Mb duplicated segment of mouse Chromosome 16. The sequence is defined by the T cell lymphoma invasion and metastasis 1 (Tiam1) gene and the interleukin 10 receptor, beta (Il10rb) gene. Hemizygous mice are fertile. This duplicated region is located on 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). Dp(16)3Yey/+ contains 17 genes orthologous to genes on Hsa21. These mice do not exhibit the heart defects associated with Down syndrome.

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 of approximately 2.11 Mb between the T cell lymphoma invasion and metastasis 1 (Tiam1) gene and the interleukin 10 receptor, beta (Il10rb) gene. The cassette placed at the proximal locus was targeted upstream of Tiam1 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 Il10rb 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, Double-targeted ES cells, containing one copy of mouse Chromosome 16 with the targeted sequence duplicated (Dp) on one homolog and the reciprocal deletion (Df) on the other homolog, were injected into C57BL/6J-Tyr^c-Brd blastocysts. The resulting chimeric mice were mated to 129Sv mice and the Dp(16)3Yey and Df(16)3Yey alleles were separated. These Dp(16)3Yey/+ mice were backcrossed to 129Sv for at least 4 generations to produce a colony. Upon arrival at The Jackson Laboratory these mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Dp(16Tiam1-Il10rb)8Yey
Name: duplication, Chr 16, Y Eugene Yu 8
MGI accession ID: MGI:5561088
Generation method: Targeted
Marker symbol: Dp(16Tiam1-Il10rb)8Yey
Marker name: duplication, Chr 16, Y Eugene Yu 8
Chromosome: 16
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: This duplication was generated by recombination between two MICER clone insertions (MHPn374h24 and MHPP321i13). The 2.1 Mb duplication spans Tiam1 to Il10rb. The duplication retains the puromycin and neomycin resistance cassettes from the original MICER clones.