EJACULATORY ABNORMALITIES IN MICE WITH TARGETED DISRUPTION OF THE GENE FOR HEME OXYGENASE-2

Nitric oxide (NO) is well established as a neurotransmitter in the cen tral and peripheral nervous systems(1). More recently, another gas, ca rbon monoxide (CO) has also been implicated in neurotransmission. In t he nervous system CO is formed by a subtype of heme oxygenase (HO) des ignated HO2 (ref. 2). HO2 is localized to discrete neuronal population s in the brain resembling localizations of soluble guanylyl cyclase, w hich is activated by CO (ref. 3). CO may also function in the peripher al autonomic nervous system, in conjunction with NO. The majority of g anglia in the myenteric plexus possess both HO2 and neuronal NO syntha se (NOS)(4). Defects in myenteric plexus neurotransmission occur both in mice with targeted deletion of genes for HO2 and neuronal NOS (ref. 5). HO2 also occurs in other autonomic ganglia including the petrosal , superior cervical and nodose ganglia(4). Neuronal NOS is localized t o neurons regulating male reproductive behavior, such as penile erecti on, and NOS inhibitors prevent erection(6). Because of the other paral lels between NO and CO, we speculated that CO may play a role in male reproductive behavior. In the present study we describe HO2 localizati on in neuronal structures regulating copulatory reflexes. Reflex activ ity of the bulbospongiosus muscle, which mediates ejaculation and ejac ulatory behavior, is markedly diminished in mice with targeted deletio n of the gene for HO2 (HO2(-)).