Augmented Chemosensitivity in Black-Eyed White Mitf mi-bw Mice, Lacking Melanocytes

Abstract

Microphthalmia-associated transcription factor (Mitf) is responsible for differentiation of melanocytes, and a recessive Mitf mutant, black-eyed white (bw) mouse, is characterized by the lack of melanocytes in the skin and inner ear. To search for the hitherto unknown roles of melanocytes, we analysed the ventilatory responses of unanaesthetized bw mice by whole body plethysmography. During air breathing, bw mice showed lower breathing frequency and larger tidal volume, compared with age-matched wild-type mice, although there was no difference in the minute ventilation. Importantly, bw mice present normal haematocrit values and red blood cell counts. We next measured the immediate ventilatory responses to acute hypoxia (10% O2) and to hyperoxic hypercapnia (10% CO2). Hypoxic and hypercapnic ventilatory responses represent the functions of the chemoreceptors in the carotid body and the brainstem, respectively. The bw mice retain the peripheral hypoxic and central hypercapnic sensing functions, but exhibited augmented ventilatory responses to both hypoxia and hypercapnia. Unexpectedly, RT-PCR analysis has shown the expression of melanocyte-specific Mitf mRNA in the brain of bw mice, suggesting the presence of leptomeningeal melanocytes. These findings suggest a functional link between skin melanocytes and the central respiratory controller that generates respiratory rhythm and pattern.