BOR - Papers in Press, published online ahead of print
February 19, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.014076
BIOLOGY OF REPRODUCTION 69, 146153 (2003)
DOI: 10.1095/biolreprod.102.014076
© 2003 by the Society for the Study of Reproduction, Inc.
Abnormal Regulation of DNA Methyltransferase Expression in Cloned Mouse Embryos1
Young Gie Chung3,
Sarayu Ratnam4,
J. Richard Chaillet4,5, and
Keith E. Latham2,3
The Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry,3 Temple University School of Medicine, Philadelphia, Pennsylvania 19140
Department of Human Genetics,4 University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Department of Pediatrics,5 The Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213
Cloning by somatic cell nuclear transfer is inefficient. This is evident in the significant attrition in the number of surviving cloned offspring at virtually all stages of embryonic and fetal development. We find that cloned preimplantation mouse embryos aberrantly express the somatic form of the Dnmt1 DNA (cytosine-5) methyltransferase, the expression of which is normally prevented by a posttranscriptional mechanism. Additionally, the maternal oocyte-derived Dnmt1o isoform undergoes little or none of its expected translocation to embryonic nuclei at the eight-cell stage. Such defects in the regulation of Dnmt1s and Dnmt1o expression and cytoplasmic-nuclear trafficking may prevent clones from completing essential early developmental events. Furthermore, aberrant Dnmt1 localization and expression may contribute to the defects in DNA methylation and the developmental abnormalities seen in cloned mammals.
1 These studies were supported by grants from the National Institutes of Health to J.R.C. (HD32940), K.E.L. (HD38381), and the Fels Institute for Cancer Research (R24 CA 8826102, 5 T32 CA0921420).
2 Correspondence: Keith E. Latham, The Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, 3307 North Broad St., Room 302, Philadelphia, PA 19140. FAX: 215 707 1454; klatham{at}unix.temple.edu
Copyright © 2003 by the Society for the Study of Reproduction.