Rad50ind floxed mutant mice may be useful when studying human chromosome instability syndromes such as Nijmegen Breakage Syndrome and ataxia-telangiectasia like disorder.
John Petrini, Memorial Sloan-Kettering Cancer Center
Rad50ind floxed mutant mice possess loxP sites flanking exons 1-2 of the RAD50 homolog (Rad50) gene. RAD50 is a component of a trimeric protein complex also containing Mre11 and Nbs1 which is involved in DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Mutations in RAD50 have been found in patients with Nijmegen Breakage Syndrome (NBS), which is characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, and intellectual disability. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1-2 deleted in cre-expressing tissues.
For example, when crossed to B6.Cg-Tg(Mx1-cre)1Cgn/J mice (Stock No. 003556), expressing poly I:C-inducible Cre recombinase, offspring contain abnormal hepatocytes and exhibit decreased hepatocyte proliferation after partial hepatectomy due to accumulation of DNA damage.
A targeting vector was designed to insert a loxP site followed by a puromycin resistance (puro) cassette upstream of exon 1, and a single loxP site downstream of exon 2 of the RAD50 homolog (Rad50) gene. The construct was electroporated into 129S7/SvEvBrd-Hprtbm2-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred with C57BL/6 females. These mice were bred to mice carrying a Gt(ROSA)26Sor(cre/ERT2) allele. Subsequently, Rad50ind mice were backcrossed at least 5 generations to C57BL/6 mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation and the cre transgene was bred out of the colony.
|Allele Name||targeted mutation 3, John H J Petrini|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Rad50, RAD50 double strand break repair protein|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||A puromycin resistance cassette with a 5' loxP site was inserted upstream of exon 1, and an additional loxP site was inserted downstream of exon 2.|
When maintaining a live colony, homozygotes may be bred together.
When using the B6.129S7(Cg)-Rad50tm3Jpt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024336 in your Materials and Methods section.