PMID- 9525495
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20061115
IS  - 0033-7587 (Print)
IS  - 0033-7587 (Linking)
VI  - 149
IP  - 4
DP  - 1998 Apr
TI  - Direct evidence that transgene integration is random in murine cells, implying 
      that naturally occurring double-strand breaks may be distributed similarly within 
      the genome.
PG  - 325-9
AB  - We have examined the distribution of illegitimate integration of a transgene 
      within the genome of cells of a murine fibroblast cell line, LTA, using 
      fluorescence in situ hybridization (FISH) analysis. The transgene vector 
      contained specific sequences for detection via FISH and a hygromycin resistance 
      gene for selection. Cells were transfected via CaPO4, and pools of 250 to 3000 
      hygromycin-resistant clones were subjected to FISH analysis. The integration of 
      the transgene was scored for chromosome morphology (acrocentric, metacentric or 
      dicentric) and position (relative to centromere or telomere). More than 90% of 
      the hygromycin-resistant clones observed involved integration of the transgene 
      singly or as multiple copies, at a single site within the genome. No bias was 
      observed for integration of the transgene in any particular chromosome morphology 
      or chromosomal position, even in the presence, within the genome, of sequences 
      homologous to the transgene. This study presents direct evidence that 
      illegitimate integration of a transgene occurs randomly in murine fibroblasts. 
      Since it is postulated that initiation of illegitimate recombination involves a 
      double-strand break (DSB), a corollary to the above results would be that 
      naturally occurring DSBs also occur randomly within the murine genome.
FAU - Dellaire, G
AU  - Dellaire G
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
FAU - Chartrand, P
AU  - Chartrand P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Radiat Res
JT  - Radiation research
JID - 0401245
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chromosome Mapping
MH  - DNA Damage
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Recombination, Genetic
MH  - Transfection
MH  - Transgenes/*genetics
EDAT- 1998/04/03 00:00
MHDA- 1998/04/03 00:01
CRDT- 1998/04/03 00:00
PHST- 1998/04/03 00:00 [pubmed]
PHST- 1998/04/03 00:01 [medline]
PHST- 1998/04/03 00:00 [entrez]
PST - ppublish
SO  - Radiat Res. 1998 Apr;149(4):325-9.