Human Molecular Genetics, Vol 8, 2211-2219, Copyright © 1999 by Oxford University Press
RM John, M Hodges, P Little, SC Barton and MA Surani
Genomic imprinting results in expression of some autosomal genes from one
parental allele only. Human chromosome 11p15, and the syntenic region on
mouse distal chromosome 7, contain several imprinted genes, including p57
(KIP2) ( CDKN1C ) and IGF2. These two genes, which are separated by >700
kb, are both implicated in the pathogenesis of Beckwith-Wiedemann syndrome.
We have shown previously that an Igf2/H19 transgene is expressed
appropriately and can imprint at ectopic chromosomal locations. To
investigate the p57 (KIP2) region, we similarly tested the imprinting and
function of a 38 kb human genomic fragment containing the p57 (KIP2) gene
in transgenic mice. This transgene showed appropriate tissue-specific
expression and transgene copy number-dependent expression at ectopic sites.
However, the levels of expression are reminiscent of that found for the
paternal allele in humans (10%). There was no change in expression levels
when the transgene was inherited from the maternal germline. These results
suggest that the cis -elements required for enhanced expression of the
maternally inherited p57 (KIP2) allele lie at a distance from the gene.
This finding has important implications for the role of this gene in the
human disease, in particular with respect to the translocation breakpoints
identified in some patients.
ARTICLES
A human p57(KIP2) transgene is not activated by passage through the maternal mouse germline
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