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Journal of Biochemistry Advance Access originally published online on January 3, 2007
Journal of Biochemistry 2007 141(3):327-333; doi:10.1093/jb/mvm035
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© 2007 The Japanese Biochemical Society.

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

Kazuhisa Takeda1, Tetsuya Adachi1,2, Feng Han1, Satoru Yokoyama1, Hiroaki Yamamoto3, Wataru Hida4 and Shigeki Shibahara1,*

1Department of Molecular Biology and Applied Physiology, and 2Department of Cardiovascular and Respiratory Medicine, Tohoku University School of Medicine, 3Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, and 4Health Administration Center, Tohoku University, Sendai, Japan

*To whom correspondence should be addressed. Tel: +81-22-717-8117, Fax: +81-22-717-8118, E-mail: shibahar{at}mail.tains.tohoku.ac.jp

Received December 6, 2006; Accepted December 25, 2006


  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.

Key Words: brain, chemosensing, heart, hypoxia, hypercapnia, lung, microphthalmia-associated transcription factor, melanocyte, ventilation

Abbreviations: bw, black-eyed white; CCHS, congenital central hypoventilation syndrome; Mitf, microphthalmia-associated transcription factor


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