Abstract:
:Lethal yellow (Ay) is a mutation at the mouse agouti (a) locus that is associated with an all-yellow coat color, obesity, diabetes, tumors in heterozygotes, and preimplantation embryonic lethality in homozygotes. Previously, we cloned and characterized the wild-type agouti gene and demonstrated that it expresses a 0.8-kb mRNA in neonatal skin. In contrast, Ay expresses a 1.1-kb transcript that is ectopically overexpressed in all tissues examined. The Ay mRNA is identical to the wild-type a transcript for the entire coding region, but the 5'-untranslated sequence of the a gene has been replaced by novel sequence. Here, we demonstrate that the novel 5' sequence in the Ay mRNA corresponds to the 5'-untranslated sequence of another gene that is normally tightly linked to a in mouse chromosome 2. This other gene (Raly) has the potential to encode a novel RNA-binding protein that is normally expressed in the preimplantation embryo, throughout development, and in all adult tissues examined. Importantly, the Ay mutation disrupts the structure and expression of the Raly gene. The data suggest that the Ay mutation arose from a DNA structural alteration that affects the expression of both agouti and Raly. We propose that the dominant pleiotropic effects associated with Ay may result from the ectopic overexpression of the wild-type a gene product under the control of the Raly promoter and that the recessive embryonic lethality may be the result of the lack of Raly gene expression in the early embryo.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Michaud EJ,Bultman SJ,Stubbs LJ,Woychik RPdoi
10.1101/gad.7.7a.1203subject
Has Abstractpub_date
1993-07-01 00:00:00pages
1203-13issue
7Aeissn
0890-9369issn
1549-5477journal_volume
7pub_type
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