Ftl, a novel gene related to ubiquitin-conjugating enzymes, is deleted in the Fused toes mouse mutation
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The dominant mouse mutation Fused toes is characterized by partial syndactyly of the limbs and thymic hyperplasia. Both morphological abnormalities were shown to be related to impaired regulation of programmed cell death. Ft/Ft embryos die in midgestation showing severe malformations of fore- and mid-brain as well as randomized situs. In Ft mice a large chromosomal deletion (about 300 kb) occurred after insertional mutagenesis. In this report we describe the identification of the first gene that has been mutated by Fused toes. The expression of the novel gene Ftl is reduced in Ft/+ mice and completely absent in Ft/Ft embryos. Analysis of the Ftl cDNA revealed an open reading frame that could code for a 32-kDa protein with similarities to ubiquitin-conjugating enzymes. Ftl transcripts with alternative 5′ UTR sequences as well as differential usage of polyadenylation sites were found. Interestingly, the 3’ parts of the longest Ftl transcripts are identical to the reverse complement of the 3′-most sequences of the Rb-related pl30 gene. Both genes are transcribed in opposite directions and overlap in their 3′ UTRs. Despite the close linkage, pl30 expression appeared not to be affected by the Ft mutation. In wild type mice, Ftl expression levels were found to be high in brain, kidney, and testes and detectable in all other adult organs and throughout embryonic development. Finally, we show that Ftl is conserved among mammals and identify the human homolog.
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