Impaired development of melanoblasts in the black-eyed white Mitf(mi-bw) mouse, a model for auditory-pigmentary disorders

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2012-06, Vol.17 (6), p.494-508
• Main Authors: Hozumi, Hiroki, Takeda, Kazuhisa, Yoshida-Amano, Yasuko, Takemoto, Yuji, Kusumi, Ryota, Fukuzaki-Dohi, Urara, Higashitani, Atsushi, Yamamoto, Hiroaki, Shibahara, Shigeki
• Format: Article
• Language: English
• Subjects: Animals; Deafness - embryology; Deafness - genetics; Deafness - metabolism; Deafness - pathology; Melanocytes - cytology; Melanocytes - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; Pigmentation Disorders - embryology; Pigmentation Disorders - genetics; Pigmentation Disorders - metabolism; Pigmentation Disorders - pathology; RNA, Messenger - metabolism; Skin - metabolism
• ISSN: 1365-2443
• DOI: 10.1111/j.1365-2443.2012.01603.x

Microphthalmia-associated transcription factor (Mitf) is a regulator for differentiation of melanoblasts that are derived from the neural crest. The mouse homozygous for the black-eyed white (Mitf(mi-bw)) allele is characterized by the white coat color and deafness, with black eye that is associated with the lack of melanocytes in skin and inner ear. The Mitf(mi-bw) mutation is an insertion of the LINE1 retrotransposable element into intron 3 of the Mitf gene that causes the selective deficiency of the melanocyte-specific Mitf isoform, Mitf-M. Here, we show the expression of Mitf-M mRNA in the trunk region of the homozygous Mitf(mi-bw)(bw) mouse at embryonic days (E) 11.5 and E12.5, but Mitf-M mRNA is undetectable at E13.5. In addition, using bw mouse that carries the lacZ transgene under the control of a melanoblast-specific promoter, we show that the number of migrating melanoblasts in bw embryos was less than 10% of that in control embryos at E11.5 and E12.5, and melanoblasts disappear by E13.5. The loss of melanoblasts in bw embryos was probably caused by apoptosis. Finally, forced expression of Mitf-M in the cultured neural tube of bw embryos ensured the differentiation of melanoblasts. Therefore, the correct dose of Mitf-M is required for the normal development of melanoblasts.