title: Impaired development of melanoblasts in the black-eyed white Mitf(mi-bw)  mouse, a model for auditory-pigmentary disorders.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hozumi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yoshida-Amano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Ryota
authors.initials: R
authors.lastname: Kusumi
authors.forename: Urara
authors.initials: U
authors.lastname: Fukuzaki-Dohi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Higashitani
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D000818:Animals; D003638:Deafness / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010859:Pigmentation Disorders / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D012333:RNA, Messenger