Disease relevance of Snrpn

• Mice carrying the Snrpn - Ube3a deletion on the paternal chromosome showed severe growth retardation, hypotonia and approximately 80% lethality before weaning [1].
• A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression [2].
• Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of gene function of the imprinted genes including Snrpn within a 2 Mb domain on chromosome 15q11-13 [3].
• Cloning and sequencing of a mouse embryonal carcinoma cell mRNA encoding the tissue specific RNA splicing protein SmN [4].
• Immunogenic properties of synthetic fragments of Sm-D protein in normal and lupus mice [5].

High impact information on Snrpn

• We show here that a 0.9-kb deletion of exon 1 of mouse Snrpn did not disrupt imprinting or elicit any obvious phenotype, although it did allow the detection of previously unknown upstream exons [6].
• Here we show that a minitransgene composed of a 200-bp Snrpn promoter/exon1 and a 1-kb sequence located approximately 35 kb upstream to the SNRPN promoter confer imprinting as judged by differential methylation, parent-of-origin-specific transcription and asynchronous replication [7].
• Deletion of the SNRPN promoter/exon 1 region (the PWS IC element) appears to impair the establishment of the paternal imprint in the male germ line and leads to PWS [8].
• A related control element was isolated in the mouse Snrpn genomic region which, when deleted on the paternally inherited chromosome, resulted in the loss of expression of all four genes and early post-natal lethality [9].
• Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely-linked Gabrb-3 locus is not subject to imprinting [2].

Biological context of Snrpn

• In this in vivo study, histone methylation and acetylation are investigated along the imprinted mouse genes Snrpn, Igf2r and U2af1-rs1 [10].
• We examined the methylation status of Snrpn during oocyte growth and maturation [11].
• Moreover, using mice with only maternal copies of Snrpn (maternal duplication for the chromosome region involved and parthenogenotes), we have shown that the gene is imprinted in all of these tissues and, generally, from the time the gene is first expressed at 7.5 days gestation [12].
• Hence, we set out to investigate the epigenetic stability of neuronal genes and analyzed DNA methylation patterns in the Snurf/Snrpn imprinted cluster in several cultured mouse ES cell lines [13].
• Maternal and paternal genomes function independently in mouse ova in establishing expression of the imprinted genes Snrpn and Igf2r: no evidence for allelic trans-sensing and counting mechanisms [14].

Anatomical context of Snrpn

• Monoallelic expression of Snrpn was observed in each blastomere at the 4-cell stage, demonstrating that the germ line, which exhibits biallelic expression of imprinted genes, must be derived from cells in which imprinting was once manifest [15].
• We have identified regions within imprinted genes that show gamete-specific methylation patterns in mature germ cells and demonstrated that maternal methylation imprints on at least one imprinted gene, Snrpn, are established during the postnatal growth phase of oogenesis [11].
• Using RT-PCR, we have established that Snrpn is further expressed at low levels in lung, liver, spleen, kidney, skeletal muscle, and gonads [12].
• Influence of in vitro manipulation on the stability of methylation patterns in the Snurf/Snrpn-imprinting region in mouse embryonic stem cells [13].
• Transfections of DMR1 and DMR2 into embryonic stem cells and injection into pronuclei of fertilized eggs reveal that embryonic cells lack the capacity to establish anew the differential methylation pattern of Snrpn [16].

Associations of Snrpn with chemical compounds

• For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5 [17].
• At Snrpn, no changes in acetylation were observed in the TSA-treated cells [18].
• Bisulfite sequencing revealed that reactivation of maternal alleles of Peg3 and Snrpn in specific tissues was accompanied by partial demethylation at their potential imprinting control regions [19].

Other interactions of Snrpn

• The Igf2r and Snrpn genes were activated by the early 4-cell stage and exhibited biallelic and monoallelic expression, respectively, throughout preimplantation development [15].
• Although Snrpn, Ipw and MBII-85 are putatively transcribed from the same promoter, the transcripts are differentially detected in neural tissues [20].
• On the other hand, the Zfp127/Snrpn locus showed such an allele-specific fractionation pattern only in F(1) hybrid mice of a cross but not in those of the reciprocal cross [21].
• To examine this possibility, we introduced sequences from the DMDs of the imprinted Igf2r, H19, and Snrpn genes into a nonimprinted derivative of the normally imprinted RSVIgmyc transgene, created by excising its own DMD [22].
• We show by RNA fluorescence in situ hybridization (FISH) that expression of Snrpn, an imprinted gene regulated by the PWS-IC, is biallelic in G9a -/- ES cells, indicating loss of imprinting [23].

Analytical, diagnostic and therapeutic context of Snrpn

• 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 [24].
• The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms [17].
• In agreement with this southern blotting of mouse DNA with SmN probes reveals bands, additional to those derived from the pseudogene, which are characteristic of an intron-containing SmN gene [25].
• Neither fragment induced a response against the whole Sm-D antigen as detected by Western blotting [5].

References