Journal article
Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids
Proceedings of the National Academy of Sciences - PNAS, Vol.97(25), pp.13702-13707
12/05/2000
Handle:
https://hdl.handle.net/2376/110112
PMCID: PMC17639
PMID: 11087830
Abstract
The bacteriophage P1 Cre/
lox
P system has
become a powerful tool for
in vivo
manipulation of the
genomes of transgenic mice. Although
in vitro
studies
have shown that Cre can catalyze recombination between cryptic
“pseudo-
lox
P” sites in mammalian genomes, to date
there have been no reports of
lox
P-site infidelity in
transgenic animals. We produced lines of transgenic mice that use the
mouse
Protamine 1
(
Prm1
) gene promoter to
express Cre recombinase in postmeiotic spermatids. All male founders
and all Cre-bearing male descendents of female founders were sterile;
females were unaffected. Sperm counts, sperm motility, and sperm
morphology were normal, as was the mating behavior of the transgenic
males and the production of two-celled embryos after mating. Mice that
expressed similar levels of a derivative transgene that carries an
inactive Cre exhibited normal male fertility. Analyses of embryos from
matings between sterile Cre-expressing males and wild-type females
indicated that Cre-catalyzed chromosome rearrangements in the
spermatids that lead to abortive pregnancies with 100% penetrance.
Similar Cre-mediated, but
lox
P-independent, genomic
alterations may also occur in somatic tissues that express Cre, but,
because of the greater difficulty of assessing deleterious effects of
somatic mutations, these may go undetected. This study indicates that,
following the use of the Cre/
lox
P site-specific
recombination systems
in vivo
, it is prudent to
eliminate or inactivate the
Cre
recombinase gene as
rapidly as possible.
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Details
- Title
- Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids
- Creators
- Edward E Schmidt - Department of Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59715; andDeborah S Taylor - Department of Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59715; andJustin R Prigge - Department of Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59715; andSheila Barnett - Department of Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59715; andMario R Capecchi - Department of Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59715; and
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.97(25), pp.13702-13707
- Academic Unit
- UNKNOWN
- Publisher
- The National Academy of Sciences
- Identifiers
- 99900547145201842
- Language
- English
- Resource Type
- Journal article