It has been hypothesized that O2sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O2sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91phox-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47phox-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 ± 18.0 vs. 20.0 ± 13.0% ( n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47phox-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47phox-null mutant than in wild-type mice: 109.61 ± 13.29 vs. 72.54 ± 7.65 impulses/s ( n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was ∼58% larger in p47phox-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91phox- and p47phox-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91phoxcomponent of the phagocytic NADPH oxidase does not alter the O2-sensing mechanism of the carotid body. However, absence of the p47phoxcomponent significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O2sensing in EPO-producing cells of the kidney appears to be independent of the gp91phoxand p47phoxcomponents of the phagocytic NADPH oxidase.
Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background
