These Rap1F 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 Rap1F mutant mice may be useful in generating conditional mutations for studying the shelterin complex of telomeres, telomere maintenance, chromosomal stability, cancer, and aging.
Titia de Lange, The Rockefeller University
Mice homozygous for this Rap1F 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 Rap1F mutant mice may be useful in generating conditional mutations for studying the shelterin complex of telomeres, telomere maintenance, chromosomal stability, cancer, and aging.
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-Tyrc-2J (aka B6(Cg)-Tyrc-2J/J ; Stock No. 000058). Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with albino C57BL/6J-Tyrc-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 Rap1F 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 Rap1F 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 Rap1F mice may still be segregating for the Tyrc-2J mutation.
|Allele Name||targeted mutation 1.1, Titia de Lange|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Terf2ip, telomeric repeat binding factor 2, interacting protein|
|Gene Synonym(s)||DRIP5; RAP1; Rap1|
|Strain of Origin||B6(Cg)-Tyr |
|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.|
|Mutations Made By|| |
Titia de Lange, The Rockefeller University
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129-Terf2iptm1.1Tdl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012346 in your Materials and Methods section.
|Heterozygous or wildtype for Terf2ip<tm1.1Tdl>|
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