title: Microphthalmia-associated transcription factor ensures the elongation of axons and dendrites in the mouse frontal cortex.
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-bwallele). Mice homozygous for the Mitfmi-bwallele 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-bwmice 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.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BRC, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Furuse
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BRC, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, RIKEN BRC, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, 980-8575, Japan.|Faculty of Sports Science, Sendai University, Shibata-Gun, Miyagi, 989-1693, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000201:enzymology; D003401:Creatine / Q000096:biosynthesis; D003404:Creatinine / Q000097:blood; D003712:Dendrites / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D020233:Gait Disorders, Neurologic / Q000235:genetics; D050937:Guanidinoacetate N-Methyltransferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000502:physiology*; D000071446:Neuronal Outgrowth / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D059467:Transcriptome
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D003404:Creatinine; C494507:Gamt protein, mouse; D050937:Guanidinoacetate N-Methyltransferase; D003401:Creatine