Microphthalmia-associated transcription factor ensures the elongation of axons and dendrites in the mouse frontal cortex

Koji Ohba, Kazuhisa Takeda, Tamio Furuse, Tomohiro Suzuki, Shigeharu Wakana, Takashi Suzuki, Hiroaki Yamamoto, Shigeki Shibahara

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Long interspersed element-1 (LINE-1) is a mammalian transposable element, and its genomic insertion could cause neurological disorders in humans. Incidentally, LINE-1 is present in intron 3 of the microphthalmia-associated transcription factor (Mitf) gene of the black-eyed white mouse (Mitfmi-bw allele). Mice homozygous for the Mitfmi-bw allele show the white coat color with black eye and deafness. Here, we explored the functional consequences of the LINE-1 insertion in the Mitf gene using homozygous Mitfmi-bw mice on the C3H background (C3H-bw mice) or on the C57BL/6 background (bw mice). The open-field test showed that C3H-bw mice moved more irregularly in an unfamiliar environment during the 20-min period, compared to wild-type mice, suggesting the altered emotionality. Moreover, C3H-bw mice showed the lower serum creatinine levels, which may reflect the creatine deficiency. In fact, morphologically abnormal neurons and astrocytes were detected in the frontal cortex of bw mice. The immunohistochemical analysis of bw mouse tissues showed the lower intensity for expression of guanidinoacetate methyltransferase, a key enzyme in creatine synthesis, in neurons of the frontal cortex and in glomeruli and renal tubules. Thus, Mitf may ensure the elongation of axons and dendrites by maintaining creatine synthesis in the frontal cortex.

Original languageEnglish
Pages (from-to)1365-1379
Number of pages15
JournalGenes to Cells
Volume21
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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