No 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. 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 DDC8, a testis-specific gene whose expression is up-regulated during spermatogenesis. Here, we demonstrate that DDC8 is not testis-specific. Furthermore, DDC8 expression in non-neural and neural tissues mimics that of TIMP-2, including its up-regulation 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 down-stream 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.

Background and Purpose-Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major contributor to mortality and morbidity following aneurysm rupture. Recently, R-type voltagedependent Ca 2+ channel (VDCC) expression has been associated with increased cerebral artery constriction in a rabbit model of SAH. The goal of the present study was to examine whether the blood component oxyhemoglobin (oxyHb) can mimic the ability of SAH to cause R-type VDCC expression in the cerebral vasculature.