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Molecular and Cellular Biology, July 2000, p. 4859-4869, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Arginine N-Methyltransferase 1 Is Required for Early
Postimplantation Mouse Development, but Cells Deficient in the Enzyme
Are Viable
Maciej R.
Pawlak,
Christina
A.
Scherer,
Jin
Chen,
Michael J.
Roshon,§ and
H.
Earl
Ruley*
Department of Microbiology and Immunology,
Nashville, Tennessee
Received 10 February 2000/Accepted 5 April 2000
Protein arginine N-methyltransferases have been
implicated in a variety of processes, including cell proliferation,
signal transduction, and protein trafficking. In this study, we have characterized essentially a null mutation induced by
insertion of the U3
Geo gene trap retrovirus into the second intron
of the mouse protein arginine
N-methyltransferase 1 gene (Prmt1). cDNAs encoding two forms of Prmt1 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. Expression of the Prmt1-
geo fusion gene was
greatest along the midline of the neural plate and in the forming head
fold from embryonic day 7.5 (E7.5) to E8.5 and in the developing
central nervous system from E8.5 to E13.5. Homozygous mutant
embryos failed to develop beyond E6.5, a phenotype consistent
with a fundamental role in cellular metabolism. However,
Prmt1 was not required for cell viability, as the protein was not
detected in embryonic stem (ES) cell lines established from mutant
blastocysts. Low levels of Prmt1 transcripts (approximately
1% of the wild-type level) were detected as assessed by a quantitative
reverse transcription-PCR assay. Total levels of arginine
N-methyltransferase activity and asymmetric
NG,NG-dimethylarginine
were reduced by 85 and 54%, respectively, while levels of
hypomethylated substrates were increased 15-fold. Prmt1 appears to
be a major type I enzyme in ES cells, and in wild-type cells, most
substrates of the enzyme appear to be maintained in a fully methylated state.
*
Corresponding author. Present address: Department of
Microbiology and Immunology, Room AA4210 MCN, Vanderbilt University
School of Medicine, 1161 21st Ave. South, Nashville, TN 37232-2363. Phone: (615) 343-1379. Fax: (615) 343-7392. E-mail:
ruleye{at}ctrvax.vanderbilt.edu.

Present address: Department of Microbiology, University of
Washington, Seattle, WA
98195.

Present address: Department of Medicine, Division of
Rheumatology, Vanderbilt University School of Medicine, Nashville,
TN
37232-2363.
§
Present address: Department of Emergency Medicine, Carolinas
Medical Center, Charlotte, NC 28232-2861.
Molecular and Cellular Biology, July 2000, p. 4859-4869, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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