B6129S-Dp(7Slx1b-Sept1)5Aam/J

Stock number: 013129
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These mutant mice possess an engineered duplication of approximately 0.39 Mb of mouse Chromosome 7, a region that shares conserved synteny with the Autism spectrum disorders critical interval on human Chromosome 16. This mutant mouse may be useful in studying Autism and other associated disorders.

Detailed description

These mutant mice possess an engineered duplication of approximately 0.39 Mb of mouse Chromosome 7. The region involved encompasses a chromosomal segment, between the GIY-YIG domain containing 2 (Giyd2) gene and the septin 1(Sept1) loci, that shares conserved synteny with Autism spectrum disorders (ASD) critical interval on human Chromosome 16, specifically the 16p11.2 region. Homozygous mutant mice are viable and fertile. These mice exhibit neuroanatomical and behavioral phenotypes. This mutant mouse may be useful in studying Autism and other associated disorders.

(Mice bearing the reciprocal deficiency mutation are also available (see Stock No. 013128)

Development

Chromosome-engineering cassettes were inserted into mouse Chromosome 7 of 129S7/SvEvBrd-Hprt1^b-m2-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 0.39 Mb between the GIY-YIG domain containing 2 (Giyd2) gene and the septin 1(Sept1) loci. The cassette placed at the distal locus contained Giyd2, a puromycin resistance gene, a loxP site, a 5' portion of an hprt minigene and an agouti transgene. The cassette placed at the distal locus contained the Sept1 gene, a tyrosinase minigene, a 3' portion of an hprt minigene, a loxP site and neomycin resistance gene. Double-targeted ES cells were subjected to transient cre recombinase expression with subsequent selection of recombinants by using hypoxanthine aminopterin thymidine (HAT) media. Correctly targeted ES cells, containing one copy of Chromosome 7 with the targeted sequence deleted (df) and one copy with the targeted sequence duplicated (dp), were injected into C57BL/6J blastocysts and the resulting chimeric mice were mated to C57BL/6J mice. The resulting offspring were genotyped and maintained as two separate lines of df and dp mice.

The dp mice were mated to C57BL/6J mice for at least two generations. Males were then sent to The Jackson Laboratory Repository. Sperm from these males were frozen. Individual aliquots of the frozen sperm were used to establish dp mice on both a mixed B6129S genetic background (Stock No. 013129) and a C57BL/6J congenic background (Stock No. 016915). For the B6129S colony, the frozen sperm aliquot was used to fertilize B6129SF1/J oocytes (Stock No. 101043). The resulting dp mice were subsequently bred to B6129SF1/J hybrid mice each generation.

Allele

Symbol: Dp(7Slx1b-Sept1)5Aam
Name: duplication, Chr 7, Alea A Mills 5
MGI accession ID: MGI:4462823
Generation method: Targeted
Attributes: Not Applicable
Synonyms: 16p11.2 dp; Dp(7)5Aam
Marker symbol: Dp(7Slx1b-Sept1)5Aam
Marker name: duplication, Chr 7, Alea A Mills 5
Chromosome: 7
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: Chromosome-engineering cassettes were inserted into mouse Chromosome 7, bracketing a span of approximately 0.39 Mb between the SMG1 homolog, phosphatidylinositol 3-kinase-related kinase (Smg1) and the aldolase A, fructose-bisphosphate (Aldoa) loci. The cassette placed at the proximal locus contained Smg1, a puromycin resistance gene, a loxP site, a 3' portion of an hprt minigene and an agouti transgene. The cassette placed at the distal locus contained the Aldoa gene, a tyrosinase minigene, a 5' portion of an hprt minigene, a loxP site and neomycin resistance gene. Double-targeted ES cells were subjected to transient cre recombinase expression with subsequent selection of recombinants by using hypoxanthine aminopterin thymidine (HAT) media to produce a duplication of the targeted region.