Transgenic systems for in vivo mutation analysis.
Transgenic mice carrying shuttle vectors containing the lacI gene as the target permit the in vivo measurement of mutations in multiple tissues and have been used to test the mutagenic effects of several compounds. Tissue-specific and time-dependent responses have been observed, and the spectrum of mutations determined by sequencing allows analysis of the role of expression time in mutagenesis. The results obtained from sequencing analysis have demonstrated spectra paralleling those observed in alternative in vivo assays. In addition to color screening, modifications to this system have permitted direct selection for mutations in the lacI target by a variety of methods. Transgenic rats containing the same lambda/lacI shuttle vector have been developed for inter-species comparison of mutagenesis testing results, which may offer a better understanding of the specific mechanisms involved in mutagenesis at the molecular level in vivo.
Provost
G S
GS
Stratagene, La Jolla, CA 92037.
Kretz
P L
PL
Hamner
R T
RT
Matthews
C D
CD
Rogers
B J
BJ
Lundberg
K S
KS
Dycaico
M J
MJ
Short
J M
JM
D000818:Animals; D010582:Bacteriophage lambda; D004252:DNA Mutational Analysis / Q000379:methods*; D004274:DNA, Recombinant / Q000032:analysis; D005038:Ethylnitrosourea / Q000633:toxicity; D005798:Genes, Bacterial / Q000187:drug effects; D005822:Genetic Vectors; D007763:Lac Operon; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D017354:Point Mutation; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
D004274:DNA, Recombinant; D012097:Repressor Proteins; D008770:Methylnitrosourea; D005038:Ethylnitrosourea