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 tra p 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 fat her showed a proportionate dwarfism phenotype, whereas the penetrance and expressivity of the phenotype was strongly reduced in Gtl2(lacZ) m ice that inherited the transgene from the mother. Gtl2 expression is h ighly similar to the beta-galactosidase staining pattern, and is downr egulated but not abolished in mice carrying the Gtl2(lacZ) insertion, In early postimplantation embryos, Gtl2 is expressed in the visceral y olk sac and embryonic ectoderm, During subsequent development and orga nogenesis, Gtl2 transcripts are abundant in the paraxial mesoderm clos ely correlated with myogenic differentiation, in parts of the central nervous system, and in the epithelial ducts of developing excretory or gans. The Gtl2 gene gives rise to various differentially spliced trans cripts, which contain multiple small open reading frames (ORF), Howeve r, none of the ATG codons of these ORFs is in the context of a strong Kozak consensus sequence for initiation of translation, suggesting tha t Gtl2 might function as an RNA. Nuclear Gtl2 RNA was detected in a te mporally and spatially regulated manner, and partially processed Gtl2 transcripts were readily detected in Northern blot hybridizations of p olyadenylated RNA, suggesting that primary Gtl2 transcripts are differ ently processed in various cell types during development. Gtl2 transcr ipt levels are present in parthenogenic embryos but may be reduced, co nsistent with the pattern of inheritance of the Gtl2(lacZ) phenotype. (C) 1998 Wiley-Liss, Inc.