B6.129S7-Dp(11Cops3-Rnf112)1Jrl/J

Stock number: 005536
Product name: Dp(11)17
Research areas: Developmental Biology Research, Neurobiology Research

Description

These mice have a rearranged chromosome carrying a duplication [Dp(11)17] of the syntenic region on mouse chromosome 11 that spans the genomic interval commonly deleted in Smith-Magenis syndrome patients.

Detailed description

Homozygous mutant mice are viable and fertile. Studies employing heterozygous mutant mice (where the duplication exists only on one chromosome) indicate that mutant mice weigh less than their wildtype litter mates. Spleens are noted to be slightly smaller than those from wild type mice. Mutant mice also exhibit impaired contextual fear conditioning. Male heterozygotes have been shown to be hyperactive in open field analysis. This mutant mouse may be useful in studies exploring the consequences of duplications involving the SMS critical interval. (Mice bearing the reciprocal deficiency mutation are also available; see Stock: 005535)

Development

Chromosome-engineering cassettes were inserted into mouse chromosome 11 of 129S5/SvEvBrd-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 3 Mb between the Cops (proximal point) and Zfp179 (distal point) loci. The cassette placed at the distal locus contained most of the Zfp179 gene (excluding exon 16), a tyrosinase minigene, a 5' portion of an hprt minigene, a loxP site and neomycin resitance gene. The cassette placed at the proximal locus contained Cops exons III to VI, a puromycin resistance gene, a loxP site, a 3' portion of an hprt minigene and a Krt1-14-agouti transgene. Double-targeted ES cells were subjected to transient cre recombinase expression with subsequent selection of recombinants buy using HAT media. Correctly targeted ES cells were injected into C57BL/6-Tyr^c-Brdblastocysts and the resulting chimeric mice were mated to C57BL/6-Tyr^c-Brd mice for nine generations before being mated to C57BL/6J at The Jackson Laboratory.

Allele

Symbol: Dp(11Cops3-Rnf112)1Jrl
Name: duplication, Chr 11, James R Lupski 1
MGI accession ID: MGI:3577256
Generation method: Targeted
Synonyms: Dp(11)17; dup(11)(Csn3-Zfp179); dup(Csn3-Zfp179)
Marker symbol: Dp(11Cops3-Rnf112)1Jrl
Marker name: duplication, Chr 11, James R Lupski 1
Chromosome: 11
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: The engineered chromosome bears a duplication of a ~3 Mb segment of Chr 11 containing 19 genes including Cops3 (a.k.a. Csn3), which only in the duplicate copy is interrupted (and inactivated) by an insertion; the entire coding region, but not the final, untranslated exon of Rnf112 (formerly Zfp179); and all the intervening DNA. The insertion in Cops3 contains a tyrosinase minigene and a transgene comprising wild-type agouti cDNA under control of the human keratin 14 promoter.