Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes

Abstract

To investigate whether ocular albinism type 1 (OA1) is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP1) and premelanosome protein (PMEL). However, the tyrosinase-related protein 2 (TRP2) level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB) was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of melanosome.

MITF-M regulates melanogenesis in mouse melanocytes

“…Interestingly, the level of Mitf is reduced in OA1 À/À or shRNAdepleted melancytes [37]. Identically, our previous work demonstrated that overexpression of OA1 in mouse melanocytes upregulated Mitf levels via the a-MSH-MC1R-cAMP-MITF signaling pathway [38].…”

TRP‑2 mediates coat color pigmentation in sheep skin

“…Constitutive and TRP-2 over-expressive melanin contents were compared on the third day following transfection. Melanin content was determined as previously described ( 22 ). Melanocytes were harvested, rinsed with PBS, and counted.…”

Exosomal miRNA derived from keratinocytes regulates pigmentation in melanocytes

“…We have found that many growth factors and genes regulate melanogenesis. For example, we found that ocular albinism type 1 protein (OA1) and glycoprotein nonmetastatic melanoma protein b (GPNMB) regulate melanogenesis in mouse melanocytes; the expression of slc45a2 and endothelin 3 are also related to sheep coat colors [4][5][6][7]; cyclin-dependent kinase 5 could regulate melanogenesis and epidermal structures [8]; and FGF21 regulates the pigmentation of alpaca melanocytes by the ERK1/2 pathway [9]. Moreover, IGF1 can modulate alpaca melanogenesis by the cAMP pathway [10].…”