TY - JOUR
T1 - Impaired development of melanoblasts in the black-eyed white Mitf mi-bw mouse, a model for auditory-pigmentary disorders
AU - Hozumi, Hiroki
AU - Takeda, Kazuhisa
AU - Yoshida-Amano, Yasuko
AU - Takemoto, Yuji
AU - Kusumi, Ryota
AU - Fukuzaki-Dohi, Urara
AU - Higashitani, Atsushi
AU - Yamamoto, Hiroaki
AU - Shibahara, Shigeki
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1365-2443.2012.01603.x
DO - 10.1111/j.1365-2443.2012.01603.x
M3 - Article
C2 - 22563733
AN - SCOPUS:84861483787
VL - 17
SP - 494
EP - 508
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 6
ER -