Analysis of murine Snrpn and human SNRPN gene imprinting in transgenic mice

The SNRPN gene is known to be expressed exclusively from the paternal allel e and to map to the critical region for the neurobehavioral disorder, Prade r-Willi syndrome (PWS). As a means to investigate the mechanism of imprinti ng for the SNRPN gene, we have sought to recapitulate the imprinted express ion of the endogenous gene. Using an 85-kb murine Snrpn clone, containing 3 3 kb of 5' and 30 kb of 3' flanking DNA, we obtained two intact transgenic lines. One line, containing two copies of the Snrpn transgene, recapitulate d the imprinted expression pattern of the endogenous locus, whereas the oth er transgenic line, containing a single copy, was expressed upon both mater nal and paternal inheritance. This suggests that a 6.6-kb region of materna l-specific DNA methylation that we have identified may be sufficient to con fer imprinted expression, but not in a copy-number independent manner. Fina lly, we produced five Lines of transgenic mice using a 76-kb human SNRPN cl one containing 45 kb and 7 I;b of 5' and 3' flanking DNA, respectively. We found all the lines were expressed upon both maternal and paternal inherita nce, regardless of copy number, suggesting that the imprinting machinery in mouse and human may have diverged.