Illegitimate cre-dependent chromosome rearrangements in transgenic mouse spermatids.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Schmidt, Edward E.; Taylor, Deborah S.; Prigge, Justin R.; Barnett, Sheila
Title Illegitimate cre-dependent chromosome rearrangements in transgenic mouse spermatids.
Date 2000-12-05
Description The bacteriophage P1 Cre/loxP 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-loxP" sites in mammalian genomes, to date there have been no reports of loxP-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 loxP-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/loxP site-specific recombination systems in vivo, it is prudent to eliminate or inactivate the Cre recombinase gene as rapidly as possible.
Type Text
Publisher National Academy of Sciences of the United States of America.
Volume 97
Issue 25
First Page 13702
Last Page 13707
Subject Chromatin; Female; Mice, Inbred C57BL; Phenotype
Subject MESH Chromosomes; Integrases; Spermatids
Language eng
Bibliographic Citation Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13702-7: Schmidt EE, Taylor DS, Prigge JR, Barnett S, Capecchi MR. Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids.. Retrieved on September 18.2006 from http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11087830.
Rights Management Copyright 2000 National Academy of Sciences of the United States of America. All right Reserved
Format Medium application/pdf
Identifier ir-main,429
ARK ark:/87278/s6d51529
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2021-05-06
ID 703013
Reference URL https://collections.lib.utah.edu/ark:/87278/s6d51529
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