Discovery of a novel, paternally expressed ubiquitin-specific processing protease gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4

Using mouse BAC clones spanning an imprinted interval of proximal mouse chr omosome 7 and the genomic sequence of the related interval of human chromos ome 19q13.4, we have identified a novel mouse gene, Usp29 (ubiquitin-specif ic processing protease 29), near two known imprinted genes, Peg3 and Ziml. Gene Usp29 is located directly adjacent to Peg3 in a "head-to-head" orienta tion, and comprises exons distributed over a genomic distance of at least 4 00 kb. A similar human gene is also Found in the homologous location in hum an chromosome 19q13.4. The mouse Usp29 gene is also imprinted and is transc ribed mainly from the paternal allele with highest expression levels in adu lt brain, especially in the cerebral cortex and hippocampus, and in the For ebrain, face, and limb buds of midgestation mouse embryos. Analysis of a fu ll-length 7.6-kb cDNA clone revealed that Usp29 encodes an 869-amino-acid p rotein that displays significant homology with yeast and nematode ubiquitin carboxyl-terminal hydrolases. These data suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase), Usp29 may represent anothe r imprinted gene involved in the ubiquitination pathway. This identificatio n of a third imprinted gene, Usp29, From the Peg3/Ziml-region confirms the presence of a conserved imprinted domain spanning at least 500 kb in the pr oximal portion of mouse chromosome 7 (Mmu7).