B6;129-Terf2ip^tm1.1Tdl/J

Stock number: 012346
Research areas: Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

These Rap1^F mice harbor loxP sites flanking exon 2 (encoding the TRF2 binding domain) of the mouse Rap1 locus (also called mRap1, TRF2-interacting factor, Terf2ip, or telomeric repeat binding factor 2 interacting protein). Telomeres serve a dual role in protecting the chromosome ends from degradation/repair activities and in intracellular signaling for regulating cell proliferation. Mammalian telomeres are formed by tandem TTAGGG sequence repeats bound by a specialized complex of six telomere-associated proteins called the shelterin complex. As Rap1 is one of the components of shelterin, these Rap1^F mutant mice may be useful in generating conditional mutations for studying the shelterin complex of telomeres, telomere maintenance, chromosomal stability, cancer, and aging.

Detailed description

Mice homozygous for this Rap1^F allele are viable and fertile, with loxP sites flanking exon 2 of the mouse Rap1 gene (also called mRap1, TRF2-interacting factor, Terf2ip, or telomeric repeat binding factor 2 interacting protein). When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the TRF2 binding domain deleted in the cre-expressing tissues. As Rap1 is one of the components of shelterin, these Rap1^F mutant mice may be useful in generating conditional mutations for studying the shelterin complex of telomeres, telomere maintenance, chromosomal stability, cancer, and aging.

Development

A targeting vector was designed to insert a frt-flanked neomycin cassette and loxP site upstream of exon 2, and a second loxP site (together with an NdeI site) downstream of exon 2 of the mouse Rap1 locus (also called mRap1, TRF2-interacting factor, Terf2ip, or telomeric repeat binding factor 2, interacting protein). The construct was electroporated into CY2.4 embryonic stem (ES) cells derived from C57BL/6J-Tyr^c-2J (aka B6(Cg)-Tyr^c-2J/J ; Stock No. 000058). Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with albino C57BL/6J-Tyr^c-2J females to establish the colony. Rap1 mutant mice were then bred to FLPe-deleter mice (B6;129 mixed genetic background; derived from Stock No. 003946) to remove the frt-flanked neo cassette. The resulting Rap1^F mice (with loxP site and single frt site remaining upstream of exon 2, and a second loxP site downstream of exon 2) were selected. Black Rap1^F mice were bred together (and the FLPe-expressing transgene was removed) for many generations, and then backcrossed at least one generation to C57BL/6J mice prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. These Rap1^F mice may still be segregating for the Tyr^c-2J mutation.

Allele

Symbol: Terf2ip^tm1.1Tdl
Name: targeted mutation 1.1, Titia de Lange
MGI accession ID: MGI:4441595
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Terf2ip
Marker name: telomeric repeat binding factor 2, interacting protein
Chromosome: 8
Strain of origin: B6(Cg)-Tyr^c-2J
Molecular note: An frt flanked neo cassette with a 3' loxP site was inserted upstream of exon 2 and an additional loxP site was inserted downstream of exon 2. Flp mediated recombination removed the neo cassette leaving exon 2 floxed.