The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA

We have isolated a novel mouse gene ( Gtl2 ) from the site of a gene trap integration ( Gtl2 lacZ ) that gave rise to developmentally regulated lacZ expression, and a dominant parental‐origin–dependent phenotype. Heterozygous Gtl2 lacZ 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 Gtl2 lacZ 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 Gtl2 lacZ 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 Gtl2 lacZ phenotype. Dev. Dyn. 1998;212:214–228. © 1998 Wiley‐Liss, Inc.