Specific expression of Gsta4 in mouse cochlear melanocytes: a novel role for hearing and melanocyte differentiation

Abstract

Mammalian pigment cells produce melanin as the main pigment. Melanocytes, one of the two types of mammalian pigment cells, differentiate from the neural crest and migrate to a variety of organs during development. Melanocytes exist not only in the skin but also in other sites such as the cochlea where they are essential for hearing. Mitf(mi-bw) is one of the known recessive alleles of the mouse microphthalmia-associated transcription factor (Mitf) locus, which is essential for the development of pigment cells. Homozygous Mitf(mi-bw)/Mitf(mi-bw) mice have a completely white coat with black eyes and are deaf due to the lack of melanocytes. By comparing gene expression profiles in cochleae of wild-type and Mitf(mi-bw)/Mitf(mi-bw) mice, we now demonstrate the specific expression of glutathione S-transferase alpha 4 (Gsta4) in the stria vascularis. Gsta4 encodes one of the cytosolic glutathione S-transferases (GSTs) which participate in detoxification processes of many tissues. This gene is specifically expressed in intermediate cells of the stria vascularis, suggesting a novel function for cochlear melanocytes. Moreover, among mammalian pigment cells, expression of Gsta4 was restricted to cochlear melanocytes, suggesting that melanocytes in various tissues differentiate from one another depending on their location.

A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II

“…It is expressed in melanocytes, osteoclasts, and mast cells, and in the melanoblast-derived intermediate cells of stria vascularis in the inner ear (Uehara et al, 2009). MITF can also modulate potassium ion circulation of endolymphatic in the inner ear (Price and Fisher, 2001;Tachibana, 2001), and produce or maintain the balance of endolymph.…”

Melanocytes contribute to the vasculature of the choroid

“…Nevertheless, we have suggested that melanogenesis is required to respond to stressful conditions, such as toxic conditions and intense noise exposure because the mouse cochlear malanocytes specifically expressed glutathione S-transferase alpha 4 (Gsta4) in the stria vascularis, which encodes one of the cytosolic glutathione S-transferases (GSTs) playing an important role in detoxification process (Uehara et al, 2009). Interestingly, neither follicular melanocytes nor choroidal melanocytes expressed Gsta4 (Uehara et al, 2009). Our study suggests that melanocytes may differentiate to express tissue-specific function(s) depending on their habitats (microenvironments).…”

“…Immunohistochemistry Immunohistochemical staining was carried out as reported previously (Uehara et al, 2009). In brief, eyecups were prepared as mentioned above and were fixed with 4% paraformaldehyde in PBS (pH 7.3) for 2 hours at room temperature.…”

Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

“…Thus, the amount of functional MITF is critical for maintaining the functions of melanocytes in humans. Likewise, Mitf-M, the mouse counterpart of human MITF-M, is essential for the development of follicular and choroidal melanocytes [3,8] and cochlear melanocytes [9,10]. The blood vessel-enriched choroid is located adjacent to the RPE that constitutes the blood-retinal barrier that protects the photoreceptors against blood-born toxicants [11].…”