title: Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2.
abstract: Nested genes are fairly common within the mammalian nervous system, yet few studies have examined whether the guest and host genes might be coordinately regulated. Tissue inhibitors of metalloproteinase (TIMPs) inhibit extracellular matrix proteolysis mediated by metzincin proteases. TIMP-2 is the only TIMP not nested within a synapsin gene. It does, however, serve as a host for differential display clone 8 (DDC8), a testis-specific gene whose expression is upregulated during spermatogenesis. Here, we demonstrate that DDC8 is not testis specific. Furthermore, DDC8 expression in nonneural and neural tissues mimics that of TIMP-2, including its upregulation in response to traumatic brain injury, suggesting a potential regulatory relationship. The most striking observation is that the TIMP-2 knockout mouse brain contains TIMP-2 mRNA encoding exons 2-5, which are downstream of DDC8, but not exon 1, which contains the signal sequence and cysteine residue required for MMP inhibition, indicating a functional knockout. That TIMP-2 transcripts in wild-type brain contain DDC8 sequence suggests alternative splicing between the two genes.
authors.affiliation: Departments of Anatomy & Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. diane.jaworski@uvm.edu
authors.forename: Diane M
authors.initials: DM
authors.lastname: Jaworski
authors.forename: Micah
authors.initials: M
authors.lastname: Beem-Miller
authors.forename: Gentian
authors.initials: G
authors.lastname: Lluri
authors.forename: Ramiro
authors.initials: R
authors.lastname: Barrantes-Reynolds
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D032041:Nested Genes / Q000235:genetics*; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C518482:DDC8 protein, mouse; D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2