FVB/NJ-Tg(Ube3a)5Mpan/J

Stock number: 036631
Product name: Ube3aOFF#5
Strain synonyms: Ube3a-2×(untagged)
Research areas: Neurobiology Research, Research Tools

Description

Ube3a OFF#5 BAC transgenic mice [also called "Ube3a-2×(untagged)"] express functional, floxed Ube3a protein in addition to endogenous Ube3a. This increased Ube3a expression models maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15) that is associated with 1-3% of cases of human autism spectrum disorder.

Detailed description

Ube3a OFF#5 BAC transgenic mice [also called "Ube3a-2×(untagged)"] express functional, floxed Ube3a protein in addition to endogenous Ube3a. The endogenous Ube3a gene is expressed only from the maternal chromosome in neurons; a result of paternal imprinting (the antisense transcript functions to silence paternal expression in brain). Because the Ube3a OFF#5 BAC transgene lacks the transcription initiation site of the antisense transcript, expression of Ube3a OFF#5 BAC is independent of parent-of-origin or sex of the animal. This increased Ube3a gene dosage models maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15) that is associated with 1-3% of cases of human autism spectrum disorder (ASD). These male mice attack intruder C57BL/6 male mice with increased total attack time and number when compared to wild type littermates.

Homozygous animals are viable and fertile, but have heightened aggression, while hemizygous mice are not aggressive. On the FVB/NJ genetic background, transgenic mice exhibit core autism-related behavior traits (impaired three chamber sociability and social vocalizations).

When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have maternal deletion of Ube3a in Cre-expressing tissues of the offspring.

Of note, a FLAG tagged, non-floxed Ube3a BAC transgenic line is available as Stock No. 019730.

Development

The Ube3a OFF#5 mouse bacterial artificial chromosome (BAC) transgene [also called "Ube3a-2×(untagged)"], containing the entire ubiquitin protein ligase E3A (Ube3a) gene, was designed to have a loxp sites flanking exons 3-5 of the Ube3a gene on the BAC. A single frt site remains just downstream of exon 5 (a remnant of the frt-flanked zeomycin resistance cassette that was removed by a FLP-expressing plasmid during the BAC recombineering). This Ube3a BAC transgene was purified and then microinjected into FVB/NJ embryos. Transgenic founder animals from line 5 were bred to FVB/NJ mice (Stock No. 001800). Heterozygous mice were bred to FVB/NJ wildtype mice for approximately 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our living colony, an aliquot of the frozen sperm was used to fertilize oocytes from FVB/NJ inbred females. A neomycin resistance (neo) cassette from an unknown source was found to be segregating with the Ube3a OFF#5 BAC Tg.

Allele

Symbol: Tg(Ube3a)5Mpan
Name: transgene insertion 5, Matthew Anderson
MGI accession ID: MGI:6754127
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: Ube3a OFF#5; Ube3a-2x (untagged)
Marker symbol: Tg(Ube3a)5Mpan
Marker name: transgene insertion 5, Matthew Anderson
Chromosome: UN
Strain of origin: FVB/NJ
Molecular note: The transgenic construct contains the entire ubiquitin protein ligase E3A (Ube3a) gene; it is designed to have a loxp sites flanking exons 3-5. A single FRT site remains just downstream of exon 5 (a remnant of the FRT-flanked zeomycin resistance cassette that was removed by a FLP-expressing plasmid during the BAC recombineering).