STOCK Tor1aip2^tm1.1Wtd/HjwJ

Stock number: 039207
Product name: Lull1-Flx
Research areas: Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Metabolism Research, Neurobiology Research

Description

These Lull1-Flx conditional knock-out mice possess loxP sites flanking exon 2 to exon 4 of the torsin A interacting protein 2 gene (Tor1aip2). These may be useful for studying nuclear envelope (NE) biology and functional studies related to dystonia.

Detailed description

Lull1-Flx mice have loxP sites flanking exon 2 to exon 4 of the torsin A interacting protein 2 gene (Tor1aip2). The protein product Tor1aip2 gene, LULL1 is localized to the endoplasmic reticulum and is one of the two known interacting proteins of the protein, TorsinA which causes the CNS-specific disease DYT1 dystonia when defective. Homozygous Lull1-Flx mice are fully viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 2 to exon 4 deleted in the Cre-expressing tissues. The donating investigator reported that Cre recombination abolished all known isoforms as assessed by western blot. Germline deletion has not been reported by the donating investigator.

When Lull1-Flx mice are crossed with liver-specific cre lines B6.Cg-Speer6-ps1^{Tg(Alb-cre)21Mgn}/J (Stock No. 003574), causes no overt phenotype. But when crossed to both with liver-specific cre lines and Tor1aip1^flox/flox (Lap1-Flx) conditional knock-out mice (Stock No. 039206), significantly worse hepatic phenotypes are observed. This line will be useful for studies of endoplasmic reticulum biology and functional studies related to dystonia.

Of note, in addition to these mice, the same donating investigator has several strains available from The Jackson Laboratory Repository; including Tor1a- mice (Stock No. 006251), Tor1a^ΔE mice (Stock No. 025637), Tor1a^flox mice  (Stock No. 025831), Tor1a^swap mutant mice (Stock No. 028099), Lap1-Flx conditional knock-out mice (Stock No. 039206), TetO(Tor1a) mice (Stock No. 037049), Tor1b^- mice (Stock No. 037047), and Tor1b overexpressing mice (Stock No. 037048).

Development

The Lull1-Flx targeting vector was designed to insert a loxP site upstream of exon 2 followed by an frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 4 of the torsin A interacting protein 2 gene (Tor1aip2). The construct was electroporated into (C57BL/6J x 129/Sv) derived embryonic stem (ES) cells Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (Stock No. 003946) to delete the neo cassette. Progeny was crossed to remove the flp-expressing transgene. The donating investigator maintained the Lull1-Flx colony on a mixed background by crossing with wildtype mice (some from other breeding cages). Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tor1aip2^tm1.1Wtd
Name: targeted mutation 1.1, William T Dauer
MGI accession ID: MGI:7610710
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: LUL-flox; Tor1aip2^fl
Marker symbol: Tor1aip2
Marker name: torsin A interacting protein 2
Marker synonyms: 1110020D10Rik; 15kDa; IFRG15; LULL1; NET9
Chromosome: 1
Strain of origin: C57BL/6J x 129
Molecular note: A loxP site was inserted upstream of exon 2 and an FRT-flanked neo cassette and loxP site were inserted downstream of exon 4 via homologous recombination. Flp-mediated recombination removed the neo cassette.