Tandemly Repeated Transgenes of the Human Minisatellite MS32 (D1S8), with Novel Mouse Gamma Satellite Integration
Overview
Affiliations
The human hypervariable minisatellite MS32 has a well characterised internal repeat unit array and high mutation rates have been observed at this locus. Analysis of MS32 mutants has shown that male germline mutations are polarised to one end of the array and frequently involve complex gene conversion-like events, suggesting that tandem repeat instability may be modulated by cis-acting sequences flanking the locus. In order to investigate the processes affecting MS32 mutation rate and mechanism, we have created transgenic mice harbouring an MS32 allele. Here we describe the organisation of eight transgenic insertions. Analysis of these transgenic loci by MVR-PCR and structural analysis of the junctions between mouse flanking DNA and the transgenic loci has shed light on mechanisms of integration and rearrangement of the tandem repeated transgenes. Sequence analysis of the mouse DNA flanking these transgenes has shown that 5 of the 8 insertions have integrated into mouse gamma satellite repeated sequence. This suggests a non-random integration of the MS32 transgene construct into the mouse genome.
McAllister R, Liu J, Woods M, Tom S, Rupar C, Barr S Mol Ther Nucleic Acids. 2014; 3:e187.
PMID: 25158091 PMC: 4221599. DOI: 10.1038/mtna.2014.39.
Mechanism of random integration of foreign DNA in transgenic mice.
Yan B, Zhao Y, Cao W, Li N, Gou K Transgenic Res. 2013; 22(5):983-92.
PMID: 23483296 DOI: 10.1007/s11248-013-9701-z.
Lentiviral vector integration profiles differ in rodent postmitotic tissues.
Bartholomae C, Arens A, Balaggan K, Yanez-Munoz R, Montini E, Howe S Mol Ther. 2011; 19(4):703-10.
PMID: 21364536 PMC: 3070105. DOI: 10.1038/mt.2011.19.
Yan B, Li D, Gou K BMC Mol Biol. 2010; 11:58.
PMID: 20707910 PMC: 2928235. DOI: 10.1186/1471-2199-11-58.
Uh M, Khattra J, Devlin R Transgenic Res. 2006; 15(6):711-27.
PMID: 16952013 DOI: 10.1007/s11248-006-9016-4.