The mouseGtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA

Abstract

We have isolated a novel mouse gene (Gtl2) from the site of a gene trap integration (Gtl2lacZ) that gave rise to developmentally regulated lacZ expression, and a dominant parental‐origin–dependent phenotype. Heterozygous Gtl2lacZ mice that inherited the transgene from the father showed a proportionate dwarfism phenotype, whereas the penetrance and expressivity of the phenotype was strongly reduced in Gtl2lacZ mice that inherited the transgene from the mother. Gtl2 expression is highly similar to the β‐galactosidase staining pattern, and is down‐regulated but not abolished in mice carrying the Gtl2lacZ insertion. In early postimplantation embryos, Gtl2 is expressed in the visceral yolk sac and embryonic ectoderm. During subsequent development and organogenesis, Gtl2 transcripts are abundant in the paraxial mesoderm closely correlated with myogenic differentiation, in parts of the central nervous system, and in the epithelial ducts of developing excretory organs. The Gtl2 gene gives rise to various differentially spliced transcripts, which contain multiple small open reading frames (ORF). However, none of the ATG codons of these ORFs is in the context of a strong Kozak consensus sequence for initiation of translation, suggesting that Gtl2 might function as an RNA. Nuclear Gtl2 RNA was detected in a temporally and spatially regulated manner, and partially processed Gtl2 transcripts were readily detected in Northern blot hybridizations of polyadenylated RNA, suggesting that primary Gtl2 transcripts are differently processed in various cell types during development. Gtl2 transcript levels are present in parthenogenic embryos but may be reduced, consistent with the pattern of inheritance of the Gtl2lacZ phenotype. Dev. Dyn. 1998;212:214–228. © 1998 Wiley‐Liss, Inc.

Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q

“…Finally, we have carried out a Northern hybridization analysis of RNA from a day-12.5 embryo using two different probes, one speci®c for the 5 H clone and another speci®c for the 3 H clone. The band patterns and fragment lengths observed were almost identical (data not shown) and the same as those shown in the report by SchusterGossler et al (Schuster-Gossler et al 1998).…”

“…Thus, it is possible that Meg3/ Gtl2 might function as an RNA. It has also been shown that long type transcripts are located in the nuclei of cells in the mouse (Schuster-Gossler et al 1998). However, as only short type transcripts were detected in the human brain, the importance of these long type transcripts is unknown.…”

Methylation analysis of the intergenic differentially methylated region of DLK1-GTL2 in human

“…11 Gtl2 probably acts as RNA transcript as no consensus sequence for translation was detected. 12 Dlk1 and Gtl2 are located within a 1 Mb imprinted cluster containing other imprinted genes such as the paternally expressed Dio3 gene, 13 a retrotransposon-like gene (Rtl1), 14 several maternally expressed non-coding RNAs, C/D small nucleolar RNAs 15 and numerous microRNAs (miRNAs). 14, 16 Paulsen et al 9 first identified a CpG-rich tandem repeat 'repeat area 1' in the intergenic (IG) region of Dlk1/Gtl2 that was conserved between mouse, human and sheep.…”

Molecular basis of imprinting disorders affecting chromosome 14: lessons from murine models

“…Firstly, insertion of a transgene array between the IG-DMR and Meg3 promoter, when paternally inherited, prevents promoter methylation, leading to reactivation of the ncRNAs in cis and concomitant reduced expression of the protein-encoding genes. Insertion on the maternally inherited chromosome causes transcriptional interference with the Meg3 promoter and reciprocal gene mis-expression (Gtl2-LacZ mice Imprinting disorders affecting chromosome 14 (Schuster-Gossler et al 1996, Schuster-Gossler et al 1998, Sekita et al 2006, Steshina et al 2006, Fig. 2C).…”

“…2C). Inheritance of a disrupted chromosome from the father mimics TS -with intrauterine growth restriction, relative macrocephaly and small placenta, failure to thrive in the early postnatal period with subsequent growth retardation into adulthood (Schuster-Gossler et al 1998, Charalambous et al 2014a. Maternal inheritance of the transgene insertion partially reproduces the gene expression pattern associated with Kagami-Ogata syndrome and causes placentomegaly, perinatal lethality and failed metabolic adaptations to postnatal life (Charalambous et al 2012).…”