Human Molecular Genetics, 2002, Vol. 11, No. 14 1659-1668
© 2002 Oxford University Press
Evidence for translational regulation of the imprinted Snurf–Snrpn locus in mice
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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Received March 13, 2002; Accepted May 13, 2002
In studies of genomic imprinting in the Prader–Willi/Angelman domain, an agouti coat color cassette was inserted into the downstream open reading frame (ORF) of the imprinted bicistronic Snurf–Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf–Snrpn, and produced a tan abdomen only when inherited paternally in otherwise-black mice. A screen for dominant epigenetic or genetic events was performed with ENU mutagenesis, using a strategy whereby variation in abdominal color was scored at weaning. One mouse with maternal origin of the fusion gene had a tan abdomen and had an imprinting defect resulting in loss of both maternal methylation and silencing of the fusion gene. One mouse with paternal origin of the fusion gene was completely yellow and was found to have an ATG-to-AAG mutation in the initiation codon of the upstream ORF encoding SNURF. Northern blotting, immunoblotting, and transfection studies indicated that the ATG-to-AAG mutation causes a 15-fold or more increase in translation of the downstream ORF in two fusion constructs, and it is likely that similar translational control affects the normal Snurf–Snrpn transcript as well.
* To whom correspondence should be addressed. Tel: +1713 7984795; Fax: +1713 7987773; Email: abeaudet{at}bcm.tmc.edu
Present address: Department of Life Science and Institute of Genetics, National Yang-Ming University, Taipei, Taiwan.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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