Insertion of long interspersed element-1 in the Mitf gene is associated with altered neurobehavior of the black-eyed white Mitfmi-bw mouse

Kazuhisa Takeda, Hiroki Hozumi, Kunihiko Nakai, Miki Yoshizawa, Hiroshi Satoh, Hiroaki Yamamoto, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Microphthalmia-associated transcription factor (Mitf) is required for the differentiation of melanoblasts of the neural crest origin. The mouse homozygous for the black-eyed white (Mitfmi-bw) allele is characterized by white-coat color and deafness with black eye, due to the loss of melanoblasts during embryonic development. The Mitfmi-bw allele carries an insertion of long interspersed element-1 (L1) in intron 3 of the Mitf gene, which may cause the deficiency of melanocyte-specific Mitf-M. Here, we show that the L1 insertion results in the generation of alternatively spliced Mitf-M mRNA species, such as Mitf-M mRNA lacking exon 3, exon 4 or both exons 3 and 4, each of which encodes Mitf-M protein with an internal deletion. Transient expression assays showed the loss of or reduction in function of each aberrant Mitf-M protein and the dominant negative effect of Mitf-M lacking exon 4 that encodes an activation domain. Thus, the L1 insertion may decrease the expression level of functional Mitf-M. Importantly, Mitf-M mRNA is expressed in the wild-type mouse brain, with the highest expression level in the hypothalamus. Likewise, aberrant Mitf-M mRNAs are expressed in the bw mouse brain. The bw mice show the altered neurobehavior under a stressful environment, suggesting the role of Mitf-M in sensory perception.

Original languageEnglish
Pages (from-to)126-140
Number of pages15
JournalGenes to Cells
Volume19
Issue number2
DOIs
Publication statusPublished - 2014 Feb

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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