A human p57(KIP2) transgene is not activated by passage through the maternal mouse germline

Genomic imprinting results in expression of some autosomal genes from one p arental allele only, Human chromosome 11p15, and the syntenic region on mou se distal chromosome 7, contain several imprinted genes, including p57(KIP2 ) (CDKN1C) and IGF2. These two genes, which are separated by >700 kb, are b oth implicated in the pathogenesis of Beckwith-Wiedemann syndrome. We have shown previously that an lgf2/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 ge nomic fragment containing the p57(KIP2) gene in transgenic mice. This trans gene showed appropriate tissue-specific expression and transgene copy numbe r-dependent expression at ectopic sites. However, the levels of expression are reminiscent of that found for the paternal allele in humans (10%), Ther e 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 a t 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.