Protease nexin I (PNI) in mouse brain is expressed from the same gene as in seminal vesicle

Protease nexin I (PNI), a serine protease inhibitor (serpin), is the most potent tissue inhibitor of thrombin. In the nervous system, PNI has been shown to participate in processes related to synaptic plasticity and neuronal survival. We assigned the human gene for PNI (P17) to chromosome 2q33-35, and to syntenic regions in mouse chromosome 1. Others showed that a similar serpin was expressed in mouse seminal vesicle, which presented the possibility of a "duplicate" gene. The data also raised controversy over the quantity of PNI mRNA expressed in the brain vs peripheral tissues, such as seminal vesicle. In order to further our investigations of PNI regulation and its influence on neuronal survival and neuroprotection, it was necessary to confirm whether the nexin observed in mouse brain samples was identical to the published protease nexin I sequences. To accomplish this, we performed DNA sequence analysis of cDNAs made from RNAs isolated from mouse forebrain and hindbrain as well as from seminal vesicle. These confirmed the identity of the mouse PNI gene (SPI4) in brain and peripheral tissues. Furthermore, Northern hybridization studies indicated that the PNI message is present at lower levels in the adult brain compared to the adult seminal vesicle. Western immunoblotting showed no differences between brain and seminal vesicle PNI proteins. The PNI cDNAs generated will serve as useful probes for the continued characterization of the serpin:protease balance as it relates to nerve cell function.