Disease relevance of IPW

• IPW (Imprinted gene in the Prader-Willi syndrome region) was isolated using the direct selection method and yeast artificial chromosomes localized to the deletion region [1].
• As is the case with SNRPN, PWS patients with 15q11-q13 deletions do not express IPW, whereas expression is normal in Angelman syndrome patients [1].
• Of note, the naturally occurring parthenogenetic-derived mature teratoma unexpectedly expressed large amounts of IPW [2].
• Lastly, the pluripotent embryonal cancer cell line Tera-2 expressed IPW at the same level before and after differentiation induced by retinoic acid, suggesting that this gene functions in a 'housekeeping' capacity throughout cell growth [2].

High impact information on IPW

• Methylation and expression studies indicate that the paternal SNRPN allele is unaffected by the translocation, while IPW and PAR1 are unexpressed [3].
• An imprinted mouse transcript homologous to the human imprinted in Prader-Willi syndrome (IPW) gene [4].
• Lack of expression of IPW may contribute to the PWS phenotype directly [1].
• Both H19 and Insulin-like growth Factor 2 (IGF2), two additional imprinted genes, also showed biallelic expression in those same tumors that demonstrated IPW biallelic expression [2].
• Biallelic expression of IPW was found in testicular germ cell tumor and bladder cancer cells, suggesting loss of imprinting in the latter case [2].

Biological context of IPW

• Recent studies of mouse models carrying a cytogenetic deletion suggest that paternal deficiency of the SNRPN-IPW interval is critical for perinatal lethality of potential relevance to PWS [5].
• The SNURF-SNRPN sense/UBE3A antisense transcription unit spans more than 460 kb and contains at least 148 exons, including the previously identified IPW exons [6].
• A systematic search for other imprinted genes in the Prader-Willi syndrome region revealed a paternally expressed transcript (IPW, for imprinted in the Prader-Willi region) and a similarly imprinted mouse homologue (Ipw) in the conserved syntenic region on mouse chromosome 7 [7].
• Differences in AW/IPW and left/right coronary artery autonomic receptors distribution and flow regulation and/or changes in cardiovascular homeostasis/coagulation, aggregation, viscosity, microcirculation, and so on connected with AMI expansion may be involved in these differences of AMI localization [8].

Anatomical context of IPW

• Previous work has demonstrated IPW expression in the human fetus and adult, with monoallelic expression in adult lymphoblasts and fibroblasts, and in fetal tissues [2].
• Exclusive paternal expression at both SNRPN and IPW was maintained in all T cell clones and correlated with maternal methylation of the intron 1 NotI site [9].
• Clonal maintenance of imprinted expression of SNRPN and IPW in normal lymphocytes: correlation with allele-specific methylation of SNRPN intron 1 but not intron 7 [9].

Other interactions of IPW

• Paternal specific expression of the known imprinted genes SNRPN (small nuclear ribonucleoprotein-associated polypeptide N gene) and IPW (imprinted gene in the Prader-Willi syndrome region) was maintained in the A9 hybrids [10].

Analytical, diagnostic and therapeutic context of IPW

• To further examine the expression of IPW, a series of experiments were carried out using RT-PCR to measure IPW expression in placentae and various fetal and tumor tissues [2].

References